UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Hydroformylation of glycals Abson, Derek 1964

You don't seem to have a PDF reader installed, try download the pdf

Item Metadata

Download

Media
[if-you-see-this-DO-NOT-CLICK]
UBC_1965_A1 A3.pdf [ 10.74MB ]
Metadata
JSON: 1.0062109.json
JSON-LD: 1.0062109+ld.json
RDF/XML (Pretty): 1.0062109.xml
RDF/JSON: 1.0062109+rdf.json
Turtle: 1.0062109+rdf-turtle.txt
N-Triples: 1.0062109+rdf-ntriples.txt
Original Record: 1.0062109 +original-record.json
Full Text
1.0062109.txt
Citation
1.0062109.ris

Full Text

HYDROFORMYLATION  OP GLYCALS  by DEREK ABSON B . S c , U n i v e r s i t y o f Birmingham, 1952 M.Sc., U n i v e r s i t y o f Birmingham, 1 9 6 1  •A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF  DOCTOR OF PHILOSOPHY i n the Department of Chemistry  We accept t h i s t h e s i s as conforming r e q u i r e d standard  September, 1964  t o the  In the  presenting  r e q u i r e m e n t s f o r an advanced  British  Columbia, I agree that  available mission  f o r reference  f o r extensive  representatives.  cation  without-my w r i t t e n  Department  of  2.  agree that  \<U>Sr  Columbia,  per-  for scholarly o r by  that.copying or p u b l i -  f o r f i n a n c i a l gain  C k £Hyu sJVty  NWY/I  I further  by the Head o f my Department  permission.  of •  s h a l l make' i t f r e e l y  copying of t h i s thesis  The U n i v e r s i t y o f B r i t i s h V a n c o u v e r 8, Canada Date  the L i b r a r y  I t i s understood  of t h i s thesis  fulfilment of  d e g r e e a t the U n i v e r s i t y  and s t u d y .  p u r p o s e s may be g r a n t e d his  this thesis i n partial  s h a l l n o t be a l l o w e d ,  ACKNOWLEDGEMENTS  I wish t o express my g r a t i t u d e to Dr. A. Rosenthal  f o r h i s constant  i n t e r e s t and encouragement  d u r i n g the course o f t h i s r e s e a r c h .  The a s s i s t a n c e  of Dr. L. D. H a l l i n the measurement and i n t e r p r e t a t i o n of n.m.r. s p e c t r a i s g r a t e f u l l y acknowledged.  Thanks  are a l s o due t o Drs. E. von R u d l o f f and P. A. J . G o r i n of the P r a i r i e R e g i o n a l L a b o r a t o r y , N.R.C., Saskatoon, f o r p r o v i d i n g r e f e r e n c e samples o f c e r t a i n compounds.  ill ABSTRACT The r e a c t i o n of 3>4-di-0-acetyl>i|D-xylal w i t h 3 moles of  s y n t h e s i s gas  dominantly  two  (CO + 2Hg) under oxo c o n d i t i o n s gave p r e -  isomeric  2,3-di-0-acetyl-l,5-anhydro-4-deoxy  h e x i t o l s , by a d d i t i o n of a hydroxymethyl the g l y c a l .  group at C - l of  The s t r u c t u r e s of the two p o l y o l s , obtained  by d e a e e t y l a t i o n of the r e a c t i o n product and  fractionation  by paper p a r t i t i o n chromatography, were completely e s t a blished.  Formation of a p a i r of enantiomeric t r i o l e t h e r s  by p e r i o d a t e cleavage and sodium borohydride r e d u c t i o n of each p o l y o l showed that they were  l,5-anhydro-4-deoxy-  h e x i t o l s , having unbranched carbon s k e l e t o n s , t h i s being shown by the proton resonance  p o s i t i o n s and  s i t i e s i n the n.m.r. s p e c t r a of the p o l y o l s . enantiomeric t r i o l was  One  intenof the  e t h e r s , having the L - c o n f i g u r a t i o n ,  prepared from a carbohydrate of known s t r u c t u r e ,  1,4-anhydro-5-deoxy-B-arabino-hex i t o1,.thereby ing  also  the c o n f i g u r a t i o n s at C-5  anhydro-4-deoxy-hexitols.  of the two  establish-  isomeric  Assignments of the  1,5-  D-arabino-  and L - x y l o - c o n f i g u r a t i o n s to the two isomers c o n f l i c t e d " ~~ ftp w i t h r e s u l t s of Q o r i n , who had p r e v i o u s l y a s s i g n e d the D-arablno- c o n f i g u r a t i o n s t o a 1,5-anhydro-4-deoxy-hexi161 which d i d not resemble  e i t h e r of our compounds.  That  these  were the D-arabino- and,L-xylo- isomers of 1 , 5 - a n h y d r o - 4 -  iv  d e o x y - h e x i t o l was proved by t h e i r c o n v e r s i o n i n t o a p a i r of i s o m e r i c l , 5 - a n h y d r o - 4 , 6 - d i d e o x y - h e x i t o l s which were i d e n t i c a l w i t h those obtained by the r e a c t i o n o f 3 , 4 - d i - O acetyl-2-deoxy-D-xylopyranosyl  c h l o r i d e w i t h methyl mag-  nesium bromide, both s e r i e s o f r e a c t i o n s a l l o w i n g no poss i b i l i t y of configurational inversions. s c r i b e d by G o r i n was subsequently t i v e t r a n s isomer,  The p o l y o l de-  shown t o be the a l t e r n a -  1,5-anhydro-4-deoxy-D-xylo-hexitol.  A concurrent study o f the s t r u c t u r e s o f the two anhydrodeoxyhexitols  was made by n u c l e a r magnetic  resonance,  and the s t e r e o c h e m i s t r y o f the L - x y l o - isomer c o u l d be a s s i g n e d from the m u l t i p l i c i t i e s o f t h e C-4 proton  signals.  The s i n g l e C-4 proton i n the deuterated analogue o f the L - x y l o - isomer  (prepared by r e a c t i n g  3,4-di-O-acetyl-D-  x y l a l w i t h carbon monoxide and deuterium) was shown t o be e q u a t o r i a l by i t s resonance  p o s i t i o n , and i t s m u l t i p l i c i t y  on deuterium-hydrogen d e c o u p l i n g , t h i s p r o v i d i n g evidence f o r c i s - a d d i t i o n t o t h e double bond o f the g l y e a l on hydroformylation. The  oxo r e a c t i o n o f 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l  has been r e i n v e s t i g a t e d , and found t o be e n t i r e l y  analogous  to those o f other g l y c a l s , g i v i n g , on d e a c e t y l a t i o n , a mixture o f 2,6-anhydro-3-deoxy-D-galacto- and D - t a l o heptitols.  These were i s o l a t e d and c h a r a c t e r i s e d , and t h e i r  V  stereochemistry  e s t a b l i s h e d by c o r r e l a t i o n w i t h the D-gluco-  isomer, whose s t r u c t u r e has been proved by X-ray a n a l y s i s . The r e a c t i o n o f 3 , 4 - d i - O - a c e t y l - D - x y l a l formylation  under hydro-  c o n d i t i o n s , l e a d i n g t o the f o r m a t i o n of a l d e -  hydes r a t h e r than a l c o h o l s , has been i n v e s t i g a t e d .  From  the r e a c t i o n o f the g l y c a l w i t h 2 moles o f s y n t h e s i s gas, two i s o m e r i c  4,5-di-0-acety1-2,6-anhydro-3-deoxy-aldehydo-  hexoses were i s o l a t e d as t h e i r c r y s t a l l i n e 2 , 4 - d i n i t r o phenylhydrazones.  These were i d e n t i f i e d by c o n v e r s i o n  of  one o f them, 4 , 5 - d l - 0 - a c e t y 1 - 2 , 6 - a n h y d r o - 3 - d e o x y - a l d e h y d o D-lyxo-hexose, t o 1 , 5 - a n h y d r o - 4 - d e o x y - D - a r a b i n o - h e x i t o l , whose s t r u c t u r e had been e s t a b l i s h e d p r e v i o u s l y .  The two  aldehydo-hexoses were a l s o o b t a i n e d when a mixture o f 2 , 3 d i - Q - a c e t y l - 1 , 5 - a n h y d r o - 4 - d e o x y - D -a r a b l n o - and L - x y l o h e x i t o l s were r e a c t e d w i t h d i m e t h y l s u l p h o x i d e and N,N'dicyclohexylcarbodiimide.  vi CONTENTS Page 1  GENERAL INTRODUCTION The  Oxo R e a c t i o n  1  (i)  Nature of the C a t a l y s t  4  Mechanism of the Oxo R e a c t i o n  5  (li) (ill)  E f f e c t of O l e f i n Structure  on Hydro10  formylation The  (i) (ii) (ill) The  16  Glycals Structure  of the G l y c a l s  Preparation  ^  o f the G l y c a l s  Reactions of the G l y c a l s  Oxo R e a c t i o n  (ii)  23  32  Hydroxymethylatioh o f 3 , 4 - d i - O - a c e t y l - D - x y l a l (i)  20  30  of Glycals  DISCUSSION A.  16  Reactants and R e a c t i o n  Conditions  32 33  F r a c t i o n a t i o n and C h a r a c t e r i s a t i o n o f Reaction  Products  37  I d e n t i f i c a t i o n o f F r a c t i o n s I and I I  4l  (iv)  Configurations  52  (v) (vl)  I d e n t i t i e s of P o l y o l s X and Y Proton Magnetic Resonance and S t e r e o chemistry of F r a c t i o n s I and I I  (lii)  o f F r a c t i o n s I and I I  77 78  vii Page B.  Anhydrodeoxyheptitols D-galactal (i) (ii) (iii) (iv) (v)  C.  (ii) (iii)  89  Reaction Conditions  QO  C h a r a c t e r i s a t i o n o f F r a c t i o n s A and B  93  S t r u c t u r e s o f F r a c t i o n s A and B  94  Stereochemistry  99  o f F r a c t i o n s A and B of Hydroxymethylation  117  of 3 , 4 - d i - O - a c e t y l - D - x y l a l  120  S t e r i c Aspects  Hydroformylation (i)  from 3 , 4 , 6 v t r i - 0 - a e e t y l -  R e a c t i o n C o n d i t i o n s and Product  Isolation  121  Reaction with 2,4-Dinitrophenylhydrazine  124  Aldehydo-hexoses by O x i d a t i o n o f H e x i t o l s  132  EXPERIMENTAL  136  General C o n s i d e r a t i o n s  136  Experimental  138  Section A  3,4-Di-O-aeetyl-D-xylal  138  B i c o b a l t Octacarbonyl  139  Hydroxymethylation  of 3 , 4 - d i - O - a c e t y l - D - x y l a l  140  C h a r a c t e r i s a t i o n o f F r a c t i o n s I and I I  142  Consumption o f P e r i o d a t e Ion  144  Enantiomeric tetritols  2-deoxy-3-0-(2-hydroxyethyl)-glycero~ ~  2-Deoxy-3-0-(2-hydroxyethyl)-L-glycero-tetritol  146 148  viii Page Attempted P r e p a r a t i o n s of 2 - d e o x y - 3 , 4 - d i - 0 - a c e t y l D - x y l o p y r a n o s y l cyanide  153  2,3-Di,-0-acetyl-l,5-anhydro-4,6-dideoxy-D-arablnoand L - x y l o - h e x i t o l s —  155  I d e n t i f i c a t i o n of P o l y o l Y from h y d r o g e n o l y s i s of methyl <x -D-glucopyranoside  160  R e a c t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l w i t h Carbon Monoxide and Deuterium -~  l6l  Experimental Section B  164  3,4,6-Tri-O-acetyl-D-galactal  164  R e a c t i o n of 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l w i t h Carbon Monoxide and HycTrogen —  166  C h a r a c t e r i s a t i o n of F r a c t i o n s A and B  167  2,6-Anhydro-3-deoxy-4,5-G-lsopropylidene-D-ta_lo_heptitol —  169  2 6-Anhydro-3-deoxy-4,5-0-isopropylidene-1,7-di0-p-tolysulphonyl-D-talo"^heptitol  170  R e a c t i o n w i t h sodium i o d i d e  170  Consumption of P e r l o d a t e  171  Enantiomeric 2 - d e o x y - 3 - 0 - ( l , 3 - d i h y d r o x y - 2 - p r o p y l ) glycero-tetritols  172  Attempted syntheses of o p t i c a l l y pure t e t r o l e t h e r s  174  2-Deoxy-3-0_-(l,3-dihydroxy-2-propyl) -L-glycerot e t r i t o l from 2 , 6 - a n h y d r o - 3 - d e o x y - D - g f u c o - h e p t i t o l  179  3  Experimental S e c t i o n C  180  H y d r o f o r m y l a t i o n of 3*4-di-£-aeetyl-D-xylal  180  Reaction with 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e  181  ix Page 182  Fraction Y 1,5-Anhydro-4-deoxy-D-arabino-hexitol Y =  from F r a c t i o n 185  P i - 0 - a c ety1-anhydrodeoxy-aldehydo-hexoses by oxicTation o f d i - O - a c e t y l - a n h y d r o d e o x y - h e x i t o l s REFERENCES  185 '  Figure  188  F o l l o w i n g page  1  82  2  86  3  97  4  113  !  - 1 GENERAL INTRODUCTION In order t o p r o v i d e a background t o subsequent  dis-  c u s s i o n o f the a p p l i c a t i o n o f the oxo r e a c t i o n t o g l y c a l s , a b r i e f review w i l l be made of the oxo r e a c t i o n o f o l e f i n s i n g e n e r a l , and o f the chemistry of the g l y c a l s , w i t h  parti-  c u l a r emphasis i n each case on s t e r e o c h e m i c a l a s p e c t s . The Oxo R e a c t i o n The r e a c t i o n o f o l e f i n s w i t h carbon monoxide and hydrogen i n the presence  of a c o b a l t c a t a l y s t i s commonly  r e f e r r e d t o as the oxo r e a c t i o n , as e a r l y experiments u s i n g ethylene as s u b s t r a t e l e d t o the formation of an a p p r e c i a b l e q u a n t i t y o f d i e t h y l ketone.  However, the r e a c t i o n o f ethy-  lene i s not t y p i c a l , and i n g e n e r a l aldehydes are the major p r o d u c t s .  or alcohols  The s t o i c h i o m e t r y o f aldehyde  f o r m a t i o n i s as shown i n equation l_s R.CH=CH.R  +  H  0  + CO  >  2  R.CH .CHR.CHO 2  1 . — 1  T h i s r e a c t i o n i s o f t e n r e f e r r e d t o as h y d r o f o r m y l a t i o n , being f o r m a l l y e q u i v a l e n t t o the a d d i t i o n o f hydrogen and a formyl group a t e i t h e r end o f the double bond.  Alcohol  f o r m a t i o n i n the oxo r e a c t i o n (equation 2) r e s u l t s from the f u r t h e r r e d u c t i o n o f aldehydes  formed by the h y d r o f o r m y l a t i o n  reaction: R.CH .CHR.CHO •+ ,6 2  >  R.CH .CHR.CHgOH g  2  - 2 As t h e r e i s no term i n g e n e r a l use t o d e s c r i b e the o v e r a l l c o n v e r s i o n of o l e f i n s to a l c o h o l s  (equation 1_ + 2)  i t is  proposed, f o r the sake of convenience, to c o i n the e x p r e s s i o n "hydrohydroxymethylation" t o d e s c r i b e -the a d d i t i o n of hydrogen and a hydroxymethyl group t o the double bond, and a b b r e v i a t e t h i s t o "hydroxymethylation" i n subsequent d i s c u s s i o n .  It  i s noteworthy that t h i s second stage (equation 2_) from a mechanistic viewpoint i s c l o s e l y r e l a t e d t o h y d r o f o r m y l a t i o n , and indeed r e q u i r e s the presence of an a p p r e c i a b l e  partial  2 p r e s s u r e of carbon monoxide , evidence that the a c t i v e c a t a l y s t i s a cobalt  carbonyl.  H i s t o r i c a l l y , the oxo r e a c t i o n developed from the w e l l known process f o r hydrocarbon s y n t h e s i s d i s c o v e r e d by F i s c h e r and Tropsch , i n which hydrogen and carbon monoxide were passed over an i r o n c a t a l y s t under c o n d i t i o n s of h i g h temperature  (400-450°)  and moderate p r e s s u r e .  I t was  observed t h a t s m a l l amounts of oxygen-containing product's 4 were o f t e n formed, and i n 1929 Smith, Hawk and  Golden  o b t a i n e d an i n c r e a s e d y i e l d of oxygenated m a t e r i a l when ethylene was  added t o the carbon monoxide-hydrogen mixture  b e f o r e p a s s i n g i t over a c o b a l t c a t a l y s t under F i s c h e r Tropsch c o n d i t i o n s .  C r e d i t f o r the development  of the oxo  r e a c t i o n as a commercial process goes l a r g e l y t o Roelen and co-workers o f Ruhrchemie A. G. i n Germany before and 5 d u r i n g World War I I . By changing the c o n d i t i o n s of the  - 3 P i s c h e r - T r o p s c h s y n t h e s i s t o g i v e a h i g h e r pressure and a lower temperature, the r e a c t i o n of ethylene w i t h water gas (equal volumes o f carbon monoxide and hydrogen) was made to y i e l d a product c o n s i s t i n g o f propionaldehyde t o g e t h e r w i t h some d i e t h y l ketone, no hydrocarbons b e i n g  formed.  F o l l o w i n g World War I I the oxo s y n t h e s i s a t t r a c t e d wide i n t e r e s t , i n p a r t i c u l a r because  of i t s wide range o f a p p l i -  c a b i l i t y i n the c o n v e r s i o n of o l e f i n s t o aldehydes and a l c o h o l s , e s p e c i a l l y the l a t t e r . between 7 5 ° and 2 0 0 ° , 100 t o 3 0 0 atmospheres  I n g e n e r a l , temperatures  and p r e s s u r e s of s y n t h e s i s gas from a r e employed, h i g h e r temperatures  b e i n g u s u a l when a l c o h o l s r a t h e r than aldehydes a r e the desired products. In s t e p w i t h the commercial  development  of the oxo"  p r o c e s s , much fundamental work has been c a r r i e d out on t h i s and r e l a t e d r e a c t i o n s c a t a l y s e d by the metal c a r b o n y l s , and  6,7,8 t h e i r chemistry has been w e l l reviewed from time t o time D e s p i t e the accumulation o f a c o n s i d e r a b l e amount o f knowl e d g e of these r e a c t i o n s , many o f the f i n e r p o i n t s o f the complex mechanisms a r e s t i l l  not known w i t h c e r t a i n t y .  In  the f o l l o w i n g pages a b r i e f survey w i l l be made o f c u r r e n t views r e g a r d i n g the nature o f the c a t a l y s t , and the probable r o l e which i t p l a y s i n the c o n v e r s i o n o f o l e f i n s t o aldehydes, and aldehydes t o a l c o h o l s .  - 4 (i)  Nature of the C a t a l y s t In the e a r l y stages of development of the oxo  i n Germany the c a t a l y s t used was Tropsch  synthesis  the c o n v e n t i o n a l F i s c h e r -  s u r f a c e c a t a l y s t , c o n s i s t i n g of a mixture  of m e t a l l i c  c o b a l t and K i e s e l g u h r , together w i t h s m a l l amounts of and magnesium o x i d e s .  thorium  I t became evident to Roelen and  co-  workers t h a t a l l the components of the F i s c h e r - T r o p s c h c a t a l y s t w i t h the e x c e p t i o n of c o b a l t were s u p e r f l u o u s , and the a c t i v e c a t a l y s t was  probably  a s o l u b l e c a r b o n y l of c o b a l t  formed by the i n s i t u r e a c t i o n of the metal w i t h gas.  T h i s was  confirmed  synthesis  by subsequent i n v e s t i g a t i o n s of  the r e a c t i o n on a l a b o r a t o r y s c a l e ' . 1  who  that  Adkins and  2  Kresk^,  i n t r o d u c e d the use of preformed d i c o b a l t o c t a c a r b o n y l  as c a t a l y s t , demonstrated t h a t the h y d r o f o r m y l a t i o n r e a c t i o n was  i n s e n s i t i v e to sulphur p o i s o n i n g , f u r t h e r evidence  the homogeneous nature of the c a t a l y s i s .  The  for  f a c t t h a t the  oxo r e a c t i o n i s c a t a l y s e d by a c o b a l t c a r b o n y l c o n t r i b u t e s to the commercial importance of the process  s i n c e the form  i n which c o b a l t i s added i s not too important,  as would be  the case w i t h a c o n v e n t i o n a l s o l i d phase c a t a l y s t .  In  p r a c t i c e , crude organic s a l t s such as the octanoate  or  naphthenate are o f t e n used.  ion i s  f i r s t reduced E  0  —>  The  d i v a l e n t cobaltous  to the metal by hydrogen, 2 H  4  +  2 e J  Co  + +  +  2 e —>  Co  3  - 5  -  and the metal then r e a c t s w i t h carbon monoxide to form d i cobalt  octacarbonyl 2 Co  8 CO  +  4 ~  Co.(CO) 2 8  Hence, the presence of both carbon monoxide and hydrogen are r e q u i r e d to convert c o b a l t s a l t s  to the c a r b o n y l .  A c o n s i d e r a b l e amount of evidenoe has  accumulated  which i n d i c a t e s t h a t c o b a l t h y d r o t e t r a c a r b o n y l , HCo(CO)^, r a t h e r than d i c o b a l t o c t a c a r b o n y l , i s e f f e c t i v e i n i n i t i a t i n g the oxo r e a c t i o n .  The h y d r o t e t r a c a r b o n y l i s formed by r e a c t i o n  of hydrogen w i t h d i c o b a l t o c t a c a r b o n y l CO (C0)Q 2  +  H  2 HCo(CO)  ^  5  4  T h i s step i s thus of fundamental importance i n that i t I n v o l v e s "the a c t i v a t i o n of molecular  h y d r o g e n , which i s t r a n s 10  f e r r e d from the gas to the l i q u i d phase.  O r c h i n and  co-  workers " ' have shown t h a t the h y d r o t e t r a c a r b o n y l i s present 1  1  under oxo Is present  c o n d i t i o n s i n the absence of o l e f l n j but when o l e f i n no c o b a l t h y d r o t e t r a c a r b o n y l i s d e t e c t a b l e (as the  c o b a l t t e t r a c a r b o n y l anion tlon  ^C o ( C—O,)^ ] ~) u n t i l N  a  hydroformyla-  of the o l e f i n i s complete, when an a p p r e c i a b l e amount of  the h y d r o t e t r a c a r b o n y l a g a i n appears In the r e a c t i o n mixture. (ii)  Mechanism of the Oxo Evidence  Reaction  f o r the mechanism of the oxo  r e a c t i o n as  - 6. c a r r i e d out under c o n d i t i o n s of h i g h temperature and i s l a r g e l y s p e c u l a t i v e , and  pressure  i s based on the r e s u l t s of r e -  a c t i o n s between o l e f i n s and c o b a l t h y d r o t e t r a c a r b o n y l a t atmospheric  pressure and temperature.  Early  1 12 13 theories ' ' d i d not take i n t o account  mechanistic  the now  i n t e r m e d i a c y of c o b a l t h y d r o t e t r a c a r b o n y l , and no  well-proven longer 12  appear t o be r e l e v a n t .  An e a r l y f i n d i n g of importance  was  that the r a t e of h y d r o f o r m y l a t l o n v a r i e d i n v e r s e l y w i t h i n crease i n the p a r t i a l pressure of carbon monoxide at hydrogen p r e s s u r e .  The  constant"  s t o i c h i o m e t r y of the r e a c t i o n of o l e -  f i n s w i t h c o b a l t h y d r o t e t r a c a r b o n y l and carbon monoxide at room temperature was  i n v e s t i g a t e d by O r c h i n and co-worker s ^ ' ^ 1  and w i t h a moderate excess  of o l e f i n  atmosphere of carbon monoxide was 2 HCo(CO)^ + CO + o l e f i n  —>  (l-pentene) under 1  found to be  Co (CO)g + aldehyde  6  2  The r e l a t i v e r a t e s of r e a c t i o n of v a r i o u s o l e f i n s under IS these c o n d i t i o n s ^ was  found to p a r a l l e l t h e i r r a t e s of  h y d r o f o r m y l a t l o n under oxo c o n d i t i o n s ^ . 1  The r e a c t i o n of  o l e f i n s w i t h c o b a l t h y d r o t e t r a c a r b o n y l at room temperature 17,18 and below was  f u r t h e r e x p l o r e d by Heck and Breslow  , on  whose work c u r r e n t views r e g a r d i n g the mechanisms of the oxo r e a c t i o n , s e p a r a t e l y d i s c u s s e d below f o r t l o n and hydrogenation,  are»largely based.  hydroformyla-  (a)  HydroformylatIon Subsequent t o the g e n e r a t i o n  c a r b o n y l by the h y d r o g e n o l y s i s  o f cobalt, h y d r o t e t r a -  of dicobalt octacarbonyl  (equation 5 ) , t h e c o n v e r s i o n o f o l e f i n s t o aldehydes i s regarded  as proceeding  tion of a  i n three d i s t i n c t  stages;  1. forma-  TT-complex between o l e f i n and c o b a l t hydro-  c a r b o n y l , which rearranges bond i s formed;  2.  so t h a t a carbon-metal slgma  i n s e r t i o n o f carbon monoxide between  metal and carbon, and  3.  hydrogenolysis  of i'fche r e s u l t i n g  complex t o g i v e an aldehyde. 17 1.  Heck and Breslow  c o n s i d e r that t h i s  stage i n v o l v e s a t l e a s t three d i s t i n c t HCo(CO)  s t e p s , as f o l l o w s  HCo(CO)  4  first  CO  R.0H=CHR R.CH=CH.R + HCo(CO).  RCH .CHR.Co(C0). 2  HOo(CO)  3J 8  RCH .CHR.Co(CO) + CO <F=^ RCHg.CHR.CotCO)^ 2  3  9  T h e i r view that c o b a l t h y d r o t r i c a r b o n y l , r a t h e r than the hydrotetracarbonyl, evidence  i s the r e a c t i v e s p e c i e s i s based on  t h a t t h e formation  of a l k y l c o b a l t tetracarbonyls  i s i n h i b i t e d by carbon monoxide; more fundamentally,  initial  complexing with o l e f i n would presumably r e q u i r e the p a r t i c i pation of a co-ordinately-unsaturated  carbonyl.  - 8 2. carbonyl  Heck and Breslow ° found that methylcobalt t e t r a absorbed e x a c t l y one  mole of carbon monoxide to  g i v e a product w i t h a strong band i n the i n f r a r e d at  1728  -1 cm  , a s s i g n e d to the a c y l c o b a l t l i n k a g e , R.CO.Co.  same i n f r a r e d a b s o r p t i o n  at reduced i n t e n s i t y was  The also  shown by s o l u t i o n s of a l k y l c o b a l t t e t r a c a r b o n y l s , i n d i c a t i n g that these complexes were i n e q u i l i b r i u m w i t h a c y l c o b a l t trlcarbonyls, RCH .CHR|.Co(CO) ^ 2  R.CH CHR.CO.Co(CO)  4  Evidence has  2  RCHg.CHR.CO.Co(CO) 10  14 , using C  - l a b e l l e d carbon monoxide, which i n -  d i c a t e s t h a t the i n s e r t e d c a r b o n y l to the m e t a l . the m i g r a t i o n  The  The  was  o r i g i n a l l y bonded  i n s e r t i o n r e a c t i o n i s thus e s s e n t i a l l y  of an a l k y l group from metal to the  atom of a c a r b o n y l 3.  3  been obtained w i t h analogous complexes of  19 manganese  GO ^  ligand.  r e a c t i o n of a c e t y l c o b a l t t e t r a c a r b o n y l  cobalt hydrotetracarbonyl  under room temperature  afforded  dlcoba.lt o c t a c a r b o n y l  yield  acetaldehyde and  with  conditions i n good  1 8  CH CO.Co(CO)^ + HCo(CO) 3  4  >  CH^HO + C o ( C 0 )  T h i s r e a c t i o n i s not, however, considered oxo  carbon  conditions  as, d e s p i t e  the f a c t that  2  Q  11  to operate under acetylcobalt  4  - 9 t e t r a c a r b o n y l i s a l s o reduced t o aldehyde by hydrogen  under  p r e s s u r e , the r e a c t i o n i s completely i n h i b i t e d by carbon monoxide.  To account f o r the f i n a l stage o f hydroformyla-  t i o n , Heck and Breslow suggest the i n t e r m e d i a c y o f eoo r d i n a t e l y - u n s a t u r a t e d a c y l c o b a l t t r i c a r b o n y l s , which a r e reduced t o alddydes by hydrogen  o r converted t o u n r e a c t i v e  t e t r a c a r b o r i y l s by carbon monoxide.  The well-known  adverse  e f f e c t o f carbon monoxide on the course o f the oxo r e a c t i o n can t h e r e f o r e be a t t r i b u t e d t o t h i s c o m p e t i t i o n . RCH .CHR.CO.Co(CO)„ + Ho — » RCH^.CHR.CHO +HCo(CO)o 12 2 3 2 5 — CO HCo(CO)o + CO ^ HCo(CO)u RCHg.CHR.CO.CoCCO)^ 0  d  If  S  3  (b)  Hydrogenation  A scheme which i s analogous t o that d e s c r i b e d above 1*7 l ft 20 f o r h y d r o f o r m y l a t i o n '* has been proposed by Marko f o r the subsequent  hydrogenation of aldehydes t o a l c o h o l s  under oxo c o n d i t i o n s  (equation 2_) . G o - o r d i n a t e l y - u n s a t u r a t e d  c a r b o n y l s a r e c o n s i d e r e d t o be t h e r e a c t i v e i n t e r m e d i a t e s ; thus, c o b a l t h y d r o t r l c a r b o n y l forms a  1\ -complex w i t h the  aldehyde, which rearranges t o an a l k o x y c o b a l t t r i c a r b o n y l (equation 1 3 ) .  Marko suggests that t h i s I s then hydro-  genolysed by m o l e c u l a r hydrogen  to give the a l c o h o l , or i s  competed f o r by carbon monoxide, g i v i n g r i s e t o an u n r e a c t i v e tetracarbonyl  - 10 -  ,H RC=0 R.CHO + HCo(CO)  R.CH 0.Co(C0)  13  HCo(C0)  14  2  3  v HCo(CO) R.CH 0,Co(CO) 2  3  + H  2  >R.CH 0H'+ 2  3  CO R.CH O.Co(CO) 2  4  21 22 The views o f A l d r i d g e and Jonassen  '  differ  from  those o f other workers i n that they regard h y d r o f o r m y l a t l o n , and hydrogenation o f aldehydes, t o be heterogeneously c a t a l y s e d r e a c t i o n s i n that the i n s i t u f o r m a t i o n o f c o b a l t h y d r o t e t r a c a r b o n y l by the h y d r o g e n o l y s i s o f d i c o b a l t octacarbonyl  (equation 5) i s c a t a l y s e d by c o b a l t  metal,  which they c o n s i d e r t o be present i n e q u i l i b r i u m w i t h t h e s o l u b l e o c t a c a r b o n y l (equation 4 ) .  T h e i r concept of the  subsequent  stages i s , however, fundamentally s i m i l a r t o 17 18 20 those o f Heck and Breslow ' and Marko 1  (iii) ( ) a  E f f e c t o f O l e f i n S t r u c t u r e on H y d r o f o r m y l a t l o n E f f e c t on Rate of R e a c t i o n All  simple o l e f i n s have been found t o undergo the  oxo r e a c t i o n , although t h e r a t e o f r e a c t i o n i s observed t o be h i g h l y dependent on t h e s t r u c t u r e o f t h e o l e f i n .  Workers  l6 at the U.S. Bureau o f Mines  have made a comprehensive  study o f t h e i n f l u e n c e o f s t r u c t u r e on the r a t e o f hydrof o r m y l a t l o n a t 1 1 0 ° , u s i n g 26 o l e f i n i c hydrocarbons, and  - 11 a 5 0 - f o l d v a r i a t i o n was slowest r a t e s .  -  observed between the f a s t e s t  The r e s u l t s i n a l l cases appear t o  and  demonstrate  a c l e a r r e l a t i o n s h i p between r e a c t i o n r a t e and degree of s t e r i c hindrance about the double bond, the l a t t e r presumably  factor  r e f l e c t i n g the ease of f o r m a t i o n of an i n t e r m e d i a t e  complex w i t h c o b a l t h y d r o t r i c a r b o n y l .  Straight chain terminal  o l e f i n s were observed t o r e a c t most r e a d i l y , w i t h l i t t l e crease i n r a t e w i t h i n c r e a s i n g c h a i n l e n g t h . s t r a i g h t c h a i n i n t e r n a l o l e f i n s was the  de-  The r a t e f o r  about one t h i r d that f o r  t e r m i n a l o l e f i n s ; however, the exact p o s i t i o n of the  double bond, p r o v i d i n g i t was on r a t e .  i n t e r n a l , had l i t t l e  influence  Branching o f the carbon c h a i n always r e s u l t e d i n  a decrease i n r e a c t i o n r a t e , even f o r o l e f i n s having a s i n g l e methyl group remote from the double bond, as i n 4 - m e t h y l - 1 pentene.  The presence o f a methyl group at one of the carbon  atoms of the double bond reduced the r a t e 1 0 - f o l d , f o r example in  going from 1-pentene to 2-methyl-l-pentene>.  r a t e s were observed w i t h branched the  The slowest  internal olefins:  thus  r a t e of h y d r o f o r m y l a t i o n of 2,3-dimethyl-2-t|utene, i n  which the double bond i s completely s u b s t i t u t e d by methyl groups, was  approximately ^-/^Qth that of an  terminal o l e f i n . are  unbranched  The r a t e s observed f o r c y c l i c  olefins  o f i n t e r e s t i n t h a t , whereas cyclopentene and  cyclo-  heptene r e a c t e d f a s t e r than the c o r r e s p o n d i n g a c y c l i c i n t e r n a l o l e f i n s , the r e a c t i o n r a t e f o r cyclohexene  was  - 12 a p p r e c i a b l y slower.  T h i s o b s e r v a t i o n has been e x p l a i n e d  0  on the b a s i s t h a t both cyclopentene and cycloheptene a r e i n a more h i g h l y s t r a i n e d s t a t e  ( s t r a i n e n e r g i e s o f 4.4 and  4.1 kcal/mole r e s p e c t i v e l y r e l a t i v e t o c y c l o h e x e n e ) . 23 Traynham  has p o i n t e d out t h a t i n a j l l known cases the more  strained i s a cyclic  s t r u c t u r e , the more r e a c t i v e i t i s i n  e l e c t r o n donating r o l e s .  One might t h e r e f o r e expect the TT  e l e c t r o n s o f cyclohexene t o be l e s s a v a i l a b l e f o r donation to the vacant (b)  d o r b i t a l s o f c o b a l t i n complex f o r m a t i o n .  E f f e c t on Mode o f A d d i t i o n In the h y d r o f o r m y l a t l o n of unsymmetrical  olefins,  a v a i l a b l e evidence i n d i c a t e s t h a t the formyl group adds t o the l e a s t h i n d e r e d s i d e of the double bond under normal c o n d i t i o n s o f h i g h temperature  and p r e s s u r e , (although t h i s  i s not n e c e s s a r i l y the case f o r r e a c t i o n s w i t h c o b a l t  hydro-  t e t r a c a r b o n y l a t room temperature "^) J thus o l e f i n s having 9 3 1  H  the s t r u c t u r e aldehyde.  R— C H = C H  2  g i v e predominantly  the t e r m i n a l  F o r example, the major product from the hydro-  .formylation of isobutylene i s isovaleraldehyde, together oil with a small proportion of t r i m e t h y l a c e t a l d e h y d e ^ . \ 3  \3  j}==CH + CO + H CH 2  3  2  >  J3H.CH .CHO+ (CH ) C.CHO . CH 2  3  3  3  - 13 Of p a r t i c u l a r i n t e r e s t  i s the d i s t r i b u t i o n of products  obtained from the a p p l i c a t i o n of the oxo r e a c t i o n to c y c l i c vinylic  e t h e r s , as these compounds are s t r u c t u r a l l y  to the g l y c a l s . pyran  The hydroxymethylation of 2 , 3 - d i h y d r o - 4 H -  ( l ) and c e r t a i n of i t s d e r i v a t i v e s has been i n v e s t i -  gated r e c e n t l y by F a l b e and K o r t e ^ . 2  performed t h e s i s gas  (190°,  under c o n d i t i o n s  The r e a c t i o n s were  300 atmospheres of syn-  (1*1))-' l e a d i n g t o the complete  c o n v e r s i o n of  aldehydes to a l c o h o l s , thereby f a c i l i t a t i n g the c a t i o n of r e a c t i o n p r o d u c t s . pyran  related  R e a c t i o n of 2 , 3 - d i h y d r o - 4 H -  ( l ) w i t h carbon monoxide and hydrogen  dominantly i n attachment  identifi-  r e s u l t e d pre-  o f the hydroxymethyl  group to  the s i d e of the double bond adjacent t o the r i n g oxygen t o g i v e 2-hydroxymethyl-tetrahydropyran  (2)  i n 78$ y i e l d *  i n a d d i t i o n ^ a s m a l l p r o p o r t i o n of 3-hydroxymethylitetrahydropyran  (3)  was  i s o l a t e d , together with a smaller  amount, of t e t r a h y d r o p y r a n (4)  r e s u l t i n g from hydrogenation  of the double bond  / ^ C H O H 2 +  CO/H2 COp^CO^;  8N)^CH 0H  16  XT  2  (3)  (2)  (4)  3$  Under s i m i l a r c o n d i t i o n s 4H-pyran (5)  gave e x c l u s i v e l y  tetrahydropyran  (6)  2-hydroxymethyl-2,3-dihydro-  2,6-bis-hydroxymethyl-  - 14  -  HObLC'Xo  17  (5)  (6)  When the carbon atom of the double bond adjacent t o the r i n g oxygen bore a methyl s u b s t i t u e n t , as i n 2 , 6 - d i m e t h y l 2,3-dihydro-4H-pyran  (7),  then the d i r e c t i o n of a d d i t i o n  was  r e v e r s e d and 3 - h y d r o x y m e t h y l - 2 , 6 - d i m e t h y l - t e t r a h y d r o p y r a n  (8)  was  i s o l a t e d , but i n lower y i e l d  C0/H  2  Co (C0)  '2 "3 220 2  (7)  18  > 8  (8)  Comparable r e s u l t s have p r e v i o u s l y been obtained by the hydroxymethylation of f u r a n ( 9 ) .  T h i s compound  r e a c t e d as a t y p i c a l conjugated d i e n e , i n that one bond was  double  hydrogenated w h i l e the o t h e r underwent the normal  26 r e a c t i o n w i t h carbon monoxide and hydrogen the hydroxymethyl group o c c u r r e d at C - 2 , alcohol  (10)  being i s o l a t e d i n 35$  +  (9)  CO + 3H,  ; a d d i t i o n of  2-tetrahydrofurfuryl  yield.  CO (C0)Q  19  2  do)  - 15  -  However, when both p o s i t i o n s adjacent to the r i n g oxygen were blocked, hydroxymethylation site.  occurred at the a l t e r n a t i v e  Thus, 2,5-ditrtethylfuran ( n )  tetrahydrofurfuryl alcohol  gave 2 , 5 - d i m e t h y l - 3 -  (12) 27  H.  '3  (12)  (11)  20  A r e a c t i o n which c l o s e l y resembles  hydroformylation  i s the h y d r o c a r b o x y l a t i o n of o l e f i n s i n the presence  of  n i c k e l carbonyl  +  ROH  —  H Ni(C0)  ~H  H  •COOR  4  •  -COOH  21  —  B i r d and co-workers.28 found r e c e n t l y t h a t s t r a i n e d o l e f i n s such as norbornene (13) atmospheric deuterated  underwent h y d r o c a r b o x y l a t i o n at  pressure and temperature. s o l v e n t s (deuterium  d e u t e r i o a c e t i c a c i d ) I t was  (14).  of  oxide, d e u t e r i o e t h a n o l and  shown t h a t (13)  into 3-exo-deuterio-bIcyclo-j^2.2.lj acid  By the use  These workers suggest  was  converted  -heptane-2-exo-carboxylic  t h a t , In h y d r o c a r b o x y l a t i o n ,  22  COOH  - 16 e l s a d d i t i o n t o o l e f i n s from the l e a s t h i n d e r e d s i d e i s probably  general.  Two groups o f w o r k e r s ^ 3 ° ^ . 2  av  Q  i n v e s t i g a t e d the p r e -  p a r a t i o n o f 6-methyl s t e r o i d s by the a p p l i c a t i o n o f the oxo r e a c t i o n t o s t e r o i d s having a double bond i n the (15).  A^-positlon  The product i n each case was the 6-<x-hydroxymethyl( 1 6 ) , and i t was concluded t h a t  allosteroid  "the oxo r e a c t i o n  23  (15)  ( i 6 r CH OH 2  under hydroxymethylation c o n d i t i o n s by a c i s a d d i t i o n " The (i)  appears t o take  place  .  Glycals Structure  of the Glycals 31 <•  The  g l y c a l s , discovered  owe t h e i r name t o F i s c h e r ' s (impure) p r e p a r a t i o n s hyde r e a c t i o n s .  i n 1913 by F i s c h e r and Zaeh  observation  of D-glucal  ,  t h a t the f i r s t  gave c h a r a c t e r i s t i c a l d e -  When i t was l a t e r r e a l i z e d that pure g l y -  c a l s a r e not a l d e h y d i e compounds, the name was f i r m l y established.  A proposal  t o systematise g l y c a l nomenclature,  - 17 at present under o f f i c i a l c o n s i d e r a t i o n ( c f r e f e r e n c e 3 2 ) , regards the g l y c a l s as 1 , 5 - a n h y d r o - d e r i v a t i v e s  of 1-enolsj  thus 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l (40) would be renamed 3,4,6-trl-0-acetyl-l,5-anhydro-2-deoxy-D-lyxo_-hexose-l-enol, G l y c a l s are c y c l i c carbohydrates the presence 2.  c h a r a c t e r i s e d by  o f a CH=CH l i n k a g e between carbon atoms 1 and  They can be regarded f o r m a l l y as d e r i v e d from the corre-  sponding  a l d o s e by removal o f two h y d r o x y l groups from ad-  jacent carbon atoms, (e.g. D - g a l a c t a l (19) from  D-galactose  ( 1 8 ) ) , and i n t h i s r e s p e c t d i f f e r from the other w e l l known c l a s s o f unsaturated carbohydrates, the g l y c o s e e n s , which s t r u c t u r a l l y a r e d e r i v e d from the corresponding aldose by -removal o f a molecule  o f water.  the s o - c a l l e d 2-hydroxyglucals  The l a t t e r group i n c l u d e s (e.g. 2-hydroxy-D-ga1acta1  ( 1 7 ) ) , o r 1 , 2 - g l y c o s e e n s , as w e l l as the 5,6-glycoseens which have an e x o c y c l i c double bond between carbon atoms  5 and 6.  ,  CH 0H  QH^OH  CH OH 2  2  —(X -H 0  OH  >H OH  24  ;  2  (18)  (19)  Aldoses which a r e epimeric a t C - 2 , such as D-glucose and D-raannose, g i v e the same g l y c a l , as asymmetry at C-2  - 18 (and C-l) i s l o s t on formation  of the double bond; the name  of the r e s u l t i n g g l y c a l i s u s u a l l y d e r i v e d from that of the more common of the two stereoisomerie  parent  aldoses.  hexoses of the D - s e r i e s  Thus the  can g i v e r i s e to  f o u r "hexals"j D - g l u c a l , D - g a l a c t a l , D - a l l a l and (no p r e p a r a t i o n s 'pentals",  of the l a t t e r two  ( D - x y l a l and D-arabinal)  f o u r D-pentoses. ~~  D-gulal  are known), and  two  are p o s s i b l e from the  With the exception  of a novel  "furanal"  32  r e p o r t e d r e c e n t l y ^ , a l l the known g l y c a l s are r i n g s t r u c t u r e s d e r i v e d from pyranose The  six-membered  sugars.  s t r u c t u r e of the best known g l y c a l , 3 * 4 , 6 - t r i -  O-acetyl-D-glucal The  eight  (20 a) was  worked out at an e a r l y s t a g e d * 3^  presence of a double bond was  demonstrated by the a d d i t i o n  CHpR /—0  of two  (20a)  R=Ac  (20b)  R = H  atoms of bromine or hydrogen; i t s p o s i t i o n , between  carbon atoms 1 and  2, was  shown by the f a c t that cleavage  with ozone l i b e r a t e d D-arabinose, formation  of the  latter  pentose a l s o p r o v i d i n g evidence that the c o n f i g u r a t i o n s of carbon atoms 3» 4 and glucose.  The  5 are unchanged from those of ID-  s t r u c t u r e s of other g l y c a l s have been proved  - 19 i n a s i m i l a r manner.  The presence of the double bond i n  the six-membered r i n g of g l y c a l s r e s u l t s i n carbon atoms 1, 2 and 3 and the r i n g oxygen atom b e i n g c o n s t r a i n e d i n t o the s o - c a l l e d h a l f - c h a i x | conformation of the ring.  cyelohexene  The presence of s u b s t i t u e n t s on the r i n g  permits  the p o s s i b i l i t y of two h a i l f - c h a i r c o n f o r m a t ^ r m ^ o r the g l y c a l s , thus, i n the case of one conformation  (21 a) f o r  3 , 4 , 6 - t r i - O - a c e t y l - D - g l u c a l , s u b s t i t u e n t s at G-3, C-5  C-4  and  are i n e q u a t o r i a l or p s e u d o - e q u a t o r i a l p o s i t i o n s ,  whereas i n the a l t e r n a t i v e conformation  (21 b) these sub-  s t i t u e n t s are In the l e s s s t a b l e a x i a l or p s e u d o - a x i a l orientations.  That 3 , 4 , 6 - t r I - O - a c e t y l - D - g l u c a l adopts  the  CHfAc OAc (21b)  (21a)  more s t a b l e h a l f - c h a i r conformation  (21 a) i n s o l u t i o n  35 was  confirmed r e c e n t l y by H a l l and Johnson  magnetic  resonance  (100 Me/s)  .  spectroscopy at h i g h r a d i o  Using proton frequency  these workers were a b l e to measure the chemical  s h i f t of each p r o t o n , and the c o u p l i n g constants between adjacent p r o t o n s , c e r t a i n of t h e i r assignments  b e i n g confirmed  - 20 by double resonance experiments.  I t was then p o s s i b l e t o  r e l a t e the c o u p l i n g constants o f adjacent r i n g protons t o t h e i r d i h e d r a l angle by a p p l i c a t i o n of K a r p l u s ' equation-^, and thus a r r i v e a t the approximate  geometry o f the r i n g .  The r e s u l t s showed that the d i h e d r a l angle between C-H(3) and C-H(4) i s approximately 1 4 0 ° , and that between C-H(4) and C-H(5) i s about  1 5 0 ° , and t h e r e f o r e confirmed that the  g l y c a l adopts the conformation  (21 a) i n s o l u t i o n .  As the  l a t t e r d i h e d r a l angle was- l e s s than 1 8 0 ° , some " f l a t t e n i n g " of the r i n g was i n d i c a t e d .  No comparable measurements have  yet been made o f the conformations o f the other a v a i l a b l e g l y c a l s ; c e r t a i n l y i t i s reasonable t o p r e d i c t that t h e h a l f - c h a i r conformation o f 3 , 4 - d l - O j - a c e t y l - D - x y l a l (22) would be analogous  t o that found f o r 3 , 4 , 6 - t r i - O - a c e t y l -  D-glucal.  (22)  (ii)  P r e p a r a t i o n of the G l y c a l s D e s p i t e the f a c t that over 50 years have elapsed s i n c e  F i s c h e r and Zach  first  synthesised 3i4i6-tri-0-acetyl-D-  g l u c a l , t h e i r procedure, w i t h minor m o d i f i c a t i o n s designed  - 21 to Improve y i e l d s , i s s t i l l  -  the only one of s i g n i f i c a n c e  f o r the p r e p a r a t i o n of g l y c a l s .  I t appears p r o b a b l e ^  F i s c h e r ' s o r i g i n a l i n t e n t i o n on t r e a t i n g a c e t y l - c x - D - g l u c o s y l bromide (23) was  7  that  2,3,4,6-tetra-0-  w i t h z i n c and a c e t i c  acid  r e d u c t i v e dehalogenation to a f f o r d a d e r i v a t i v e of  1,5-  a n h y d r o - D - g l u c i t o i ; i n a c t u a l f a c t a good y i e l d of 3 , 4 , 6 tri-O-aeetyl-D-glucal  (20 a) was  obtained,  25  Zn/AcOH  (20a)  AcO (23) A mechanism to e x p l a i n g l y c a l formation has been  suggested  by P r i n s ^ , and d i s c u s s e d by Overend and Stacey3°\ 8  carbonium i o n i n t e r m e d i a t e (25)  r e s u l t i n g from  The  ionisation  of the acetobromoaldose (24) can e i t h e r r e a c t w i t h s o l v e n t t o g i v e the a c e t y l a t e d aldose  (26),  or can a c q u i r e  (27),  e l e c t r o n s from the metal to f u r n i s h the carbanion which a f f o r d s the g l y c a l by e l i m i n a t i o n of an group from C - 2 . may  two  acetoxy  I t i s a l s o c o n c e i v a b l e t h a t the  carbanion  a c q u i r e a proton to g i v e the 1 , 5 - a n h y d r o a l d i t o l  (29)i  although the l a t t e r do not appear to have been d e t e c t e d as products of t h i s  reaction.  - 22 -  H-C-Br  -ft  H-j-OAc (24)  H- £ 7 *  9  I H-C-OAc  * H-C-OAc  H-O-OAc  • ? •  1  (25)  (26)  2e  26  R=OH or  OAc  2  I  ^  HC  -C^OAc 0  6  (28)  (27)  (29)  . o I  Because of the Importance of g l y c a l s as i n t e r m e d i a t e s i n carbohydrate chemistry, i n p a r t i c u l a r i n the p r e p a r a t i o n of 2-deoxy s u g a r s ^ , v a r i o u s m o d i f i c a t i o n s t o F i s c h e r ' s o r i g i n a l procedure have been i n t r o d u c e d w i t h the o b j e c t of improving the o v e r a l l y i e l d s acetobromoaldose  —>  glycal  of the sequence:  —>  2-deoxy-aldose.  standard method f o r the p r e p a r a t i o n of was  aldose—> A  acetobromoaldbses  passage of hydrogen bromide through a s o l u t i o n  pension of the aldose i n a c e t i c  anhydride.  A significant  improvement over the d i r e c t use of hydrogen bromide i n t r o d u c e d by B a r c z a i - M a r t o s and Korosky  or sus-  , who  was  generated  the gas i r i s i t u by adding phosphorus t r i b r o m i d e and water, or more simply phosphorus,•.•\toi?6mlne of the f u l l y - a c e t y l a t e d  and water>- t o -a s o l u t i o n  aldose In a c e t i c  anhydride.  y i e l d s of s e v e r a l c r y s t a l l i n e acetobromoaldoses t a i n e d i n t h i s way,  Good  were ob-  without Intermediate i s o l a t i o n of the  fully-acetylated precursors.  - 23 Various  -  m o d i f i c a t i o n s have been made to F i s c h e r ' s  o r i g i n a l procedure f o r r e d u c t i o n of the acetobromo-sugar 4l w i t h z i n c and a c e t i c a c i d . troduced  Deriaz and  co-workers  in-  the use of c h l o r o p l a t i n i c a c i d which, added at  i n t e r v a l s to the r e d u c t i o n mixture, maintained a r e a c t i o n and  enabled lower temperatures to be  vigorous  employed.  S i g n i f i c a n t improvements i n the y i e l d s of 3 , 4 - d i - 0 - a cety1-D4T I — lip arabinal and 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l were a t t a i n e d i n t h i s way.  I s e l i n and R e i c h s t e i n ^ ^ added sodium a c e t a t e  t o b u f f e r the z i n c - a c e t i c a c i d mixture and  to remove hydrogen  bromide formed d u r i n g the course of the r e a c t i o n , and the z i n c by a d d i t i o n of copper as the s u l p h a t e .  The  activated most con-  venient  g e n e r a l procedure f o r g l y c a l p r e p a r a t i o n i s that of 44 45 H e l f e r i c h and co-workers ' , who combined the advantages of the acetobromoaldose p r e p a r a t i o n of Barczai-Martos  and  40 Korosky  , and  the r e d u c t i o n procedure of I s e l i n  and  43 Reichstein  * the c o n v e r s i o n  i s c a r r i e d through i n one mediates. (iii) Reactions  of aldose  to a c e t y l a t e d g l y c a l  stage without i s o l a t i o n of  inter-  of the G l y c a l s  P r a c t i c a l l y a l l the r e a c t i o n s of the g l y c a l s have t h e i r counterpart  i n w e l l known r e a c t i o n s of o l e f i n s i n  g e n e r a l , i n v o l v i n g a d d i t i o n across the double bond. m a j o r i t y of cases the d i r e c t i o n of a d d i t i o n i s  In  the  Influenced  - 24 by the p r o x i m i t y  o f the r i n g oxygen atom.  G l y c a l s r e a c t as  t y p i c a l v i n y l e t h e r s , and f r e q u e n t l y e x h i b i t an i n t e r e s t i n g resemblance t o the six-membered c y c l i c v i n y l e t h e r ,  2,3-dihydro-  4H-pyran ( l ) . T y p i c a l e l e c t r o p h i l i c a d d i t i o n t o a v i n y l  ether  r e s u l t s i n a d d i t i o n of the e l e c t r o p h i l e t o the carbon o f the double bond  (i  to the ether oxygen, as the r e s u l t i n g c a t i o n  i s s t a b i l i s e d by the e l e c t r o n - r i c h oxygen. formation  of the w e l l known t e t r a h y d r o p y r a n y l  thus proceeds as f o l l o w s  The  Acid-catalysed ethers  (30)  46  r i n g oxygen o f g l y c a l s Is seen t o exert a s i m i l a r d i r e c t -  i n g I n f l u e n c e on the course of a d d i t i o n s t o the double bond; moreover, s t e r i c f a c t o r s due t o s u b s t i t u e n t s a t C-3 appear to have a marked e f f e c t i n determining isomeric  products.  the d i s t r i b u t i o n of  Examples can be taken from a v a r i e t y of  a d d i t i o n r e a c t i o n s o f g l y c a l s to i l l u s t r a t e these p o i n t s . I o n i c a d d i t i o n s of reagent o f the g e n e r a l (where X =0H, alkoxy,  form HX 1  halogen) t o the double bond o f g l y c a l s  are w e l l known r e a c t i o n s f o r the p r e p a r a t i o n  o f 2-deoxy  aldoses  - 25 and t h e i r d e r i v a t i v e s .  The a c i d - c a t a l y s e d a d d i t i o n of water  to a f f o r d 2-deoxy sugars has been s t u d i e d i n d e t a l l 3 9 ; t y p i c a l l y the c o n v e r s i o n i s e f f e c t e d i n c o l d , d i l u t e acid solution.  I t was  c o n s i d e r e d by I s b e l l and Plgman^  under these c o n d i t i o n s 2-deoxy-D-galactose D-galactal  (19)  sulphuric  was  that  7  formed from  v i a an Intermediate sulphate e s t e r which  was  subsequently h y d r o l y s e d on h e a t i n g w i t h barium carbonate J however, t h i s was  d i s p r o v e d by Overend and co-workers  48  .  a l t e r n a t i v e 'mechanism i n v o l v i n g p r o t o n - c a t a l y s e d opening the oxygen b r i d g e has been suggested  4Q  •. 7  An of  The accepted mechan-  ism of e l e c t r o p h l l i c a d d i t i o n t o v i n y l ethers  46  , exemplified  by the f o r m a t i o n of t e t r a h y d r o p y r a n y l e t h e r s (30)  (equation  27)  would appear t o be a p p l i c a b l e to t h i s and o t h e r i o n i c a d d i t i o n s of HX-type reagents to g l y c a l s . Gis A d d i t i o n s to the Double Bond The r e a c t i o n of o l e f i n s w i t h n i t r c s y l c h l o r i d e , w i t h the f o r m a t i o n of n i t r o s o - d e r i v a t i v e s , has been c o n s i d e r e d ^ to proceed by an i o n i c mechanism, w i t h the n i t r o s o group e n t e r i n g i n t o combination as an e l e c t r o p h l l i c  fragment  and the c h l o r i n e as n u c l e o p h i l i c C l ~ . Meinwald and  N|Q, +  co-  51 workers  have o b t a i n e d experimental evidence from a study  of the r e a c t i o n s of norbornene and norbornadiene  with n i t r o -  s y l c h l o r i d e which c a s t s doubt on the i o n i c mechanism (apparent c i s a d d i t i o n , l a c k of i n c o r p o r a t i o n of n u c l e o p h i l i c  - 26 solvent).  -  They suggest a f o u r - c e n t r e  mechanism of  w i t h l i t t l e or no carbonium i o n c h a r a c t e r  addition  developing i n  the t r a n s i t i o n s t a t e  8-  Serfontein  and  c o - w o r k e r s 5 2 have obtained h i g h l y c r y s t a l l i n e  adducts by the r e a c t i o n of n i t r o s y l c h l o r i d e w i t h  various  acetylated  proton  glycals.  S t r u c t u r a l i n v e s t i g a t i o n s by  magnetic resonance spectroscopy confirmed that to the double bond was  cis.  O-acetyl-D-glucal ( 2 0 a ) ,  The  f a c t that from  (31)  was  (i -D-arabinopyranosyl c h l o r i d e  from the a d d i t i o n of n i t r o s y l c h l o r i d e to D-arabinal  3,4,6-tri-  3,4,6-tri-0-acetyl-2-deoxy-2-  nitroso-oc-D-glucopyranosyl chloride whereas the  addition  obtained, (33)  resulted  3,4-di-O-acetyl-  (32), would seem to i n d i c a t e that the C-3  group i n f l u e n c e s  acetoxy  the d i r e c t i o n of approach of n i t r o s y l  c h l o r i d e to the double bond.  CH 0Ac  CHpAc  2  O  N0C1  AcO  )Ac  AcO  N  OAc  Jt\ N=0  (20a)  (3D  28  - 27  -  N0C1  29  AcO'  AcO OAc (32)  The  l i g h t - c a t a l y s e d r e a c t i o n of o l e f i n s  with 53  phenanthraquinone to give 1,4-dioxane d e r i v a t i v e s ^ a p p l i e d to the g l y c a l s by H e l f e r i c h r ^ . a c e t y l - D - g l i | c a l (20 a) was quinone and  When  was  3,4,6-tri-O-  thus r e a c t e d w i t h phenanthra-  the r e s u l t i n g adduct d e a c e t y l a t e d , phenenthrene-  hydroquinone-D-glucoside anhydride which D-glueose (35)  was  t h a t no D-mafnnose was  (34)  was  obtained,  l i b e r a t e d on o z o n o l y s i s .  The  from fact  obtained from these r e a c t i o n s i n d i c a t e s  that a d d i t i o n of phenanthraquinone to the double bond of the g l y c a l took p l a c e e x c l u s i v e l y from the l e a s t  hindered  side  CH 0H 2  AcO  S i m i l a r l y , c i s h y d r o x y l a t l o n of the double bond of D-glu'cal (20 b) and  3 , 4 , 6 - t r i - O - a c e t y l - D - g l u c a l (20 a)  by  - 28 osmium t e t r o x i d e , proceeding osmic a c i d (equation 31)  r e s u l t e d i n predominant  of the c y c l i c i n t e r m e d i a t e the double bond, and D-mannose was  through the c y c l i c d i e s t e r of formation  at the l e a s t hindered  s i d e of  i n both cases more D-glucose than  55 obtained on hydrolysis"^  —  HO.  (b)  31  Trans A d d i t i o n s to the Double Bond Although l e s s r e l e v a n t i n c o n s i d e r i n g p o s s i b l e s t e r l e  e f f e c t s l i k e l y to be o p e r a t i v e i n the h y d r o f o r m y l a t l o n  of  g l y c a l s , a number of r e a c t i o n s i n v o l v i n g tlyglns a d d i t i o n a c r o s s the double bond of a c e t y l a t e d g l y c a l s are known i n which a s i m i l a r d i r e c t i n g i n f l u e n c e appears to be by the C-3  acetoxy s u b s t i t u e n t .  are c o n s i d e r e d  The  exerted  reactions i n question  to proceed through c y c l i c  intermediates  which  open by rearward a t t a c k of a n u c l e o p h i l e to g i v e a t r a n s product.  I t i s known that i n c y c l i c  s t e r i c course  systems the p r e f e r r e d  of t r a n s a d d i t i o n i s such as to favour  the  56 d i a x i a l product  .  Thus, In the case of the g l y c a l s , where  n u c l e o p h i l i c a d d i t i o n i s at C - l , t r a n s d i a x i a l opening of a c y c l i c intermediate  r e q u i r e s that the l a t t e r be i n a  - 29 ^-orientation  (above the plane of the r i n g ) ( 3 6 ) .  Con-  v e r s e l y , a t r a n s - d l e q u a t o r i a l product must a r i s e from a cyclic  i n t e r m e d i a t e (37)  which i s o r i e n t e d below the plane  of the p y r a n o i d r i n g  (37) The a d d i t i o n of mercuric s a l t s to o l e f i n s i s u s u a l l y c o n s i d e r e d to proceed v i a a mercurinium  i o n (e.g.  (38)),  which r e a c t s w i t h n u c l e o p h i l i c s o l v e n t t o g i v e a t r a n s product^.  From 3 , 4 , 6 - t r i - O - a c e t y l - D - g l u c a l (20 a ) , 58  Manolopoulos and co-workers^  —  o b t a i n e d , on r e a c t i o n w i t h  mercuric a c e t a t e i n methanol, a c r y s t a l l i n e compound f i e d as methyl  identi-  3,4,6-tri-0-acetyl-2-acetoxymercuri-2-deoxy-  &_D-glucopyranoside  (39),  the trans-di'^'quatorial product  - 30 These workers b e l i e v e t h a t the bulky C-3  acetoxy group tends  t o s h i e l d the double bond from a t t a c k at the upper s i d e , and  the  cx_mercurinium i o n (38)  becomes  important.  Rearward approach of methanol to C - l then leads to  through analogous mechanism, i n which the forma-  t i o n of an equal or major p r o p o r t i o n of the l e s s favoured (C-2  (39).  3,4,6-tri-O-acetyl-D-glucal  Other r e a c t i o n s of proceeding  (^)  product  having  the  kinetically  D-gluco-configuration  e q u a t o r i a l s u b s t i t u e n t ) i n d i c a t e s the importance of  a c y c l i c intermediate  at the l e a s t hindered  the r i n g , are w i t h perbenzoic  (oc) s i d e of  a c i d ( v i a 1,2-epoxide)-* ^ 0  w i t h bromine ( v i a bromonium ion)  60  , and w i t h i o d i n e 6l  and  s i l v e r benzoate ( v i a iodiniura ion) The  Oxo  Reaction  of G l y c a l 3  The r e a c t i o n of g l y c a l s w i t h carbon monoxide and hydrogen under oxo c o n d i t i o n s was f i r s t explored i n 1956 62,63,64 by Rosenthal and  co-workers  .  3,4,6-tri-0-acetyl-D-galactal D-glucal  G l y c a l s s t u d i e d were  (40) and  3,4,6-tri-O-acetyl-  (20 a ) ; i n each case s a t u r a t e d seven carbon com-  pounds were obtained and  AcO,  characterized.  CHpAc  OAc  (40)  ;  - 31 The oxo r e a c t i o n o f g l y c a l s t h e r e f o r e r e p r e s e n t e d an a d d i t i o n a l  62 method f o r l e n g t h e n i n g the carbon c h a i n of carbohydrates  .  The products obtained from these r e a c t i o n s were a c e t y l a t e d a l c o h o l s , r a t h e r than aldehydes, and undoubtedly arose by the i n i t i a l h y d r o f o r m y l a t i o n o f the g l y c a l double bond, f o l l o w e d by r e d u c t i o n o f t h e formyl group t o hydroxymethyl (equations IL and 2 ) .  The s t r u c t u r e s of the products thus  obtained were not e s t a b l i s h e d , but i n the case o f the r e a c t i o n o f 3,4,6-tri-o_-acetyl-D-galaetal i t was thought  that  hydroxymethylation had o c c u r r e d a t C-2 of the g l y c a l , t o  63 g i v e a branched-chain carbohydrate appeared  ;  this glycal also  t o be unique i n t h a t o n l y one product was i s o l a t e d  from i t s r e a c t i o n w i t h carbon monoxide and hydrogen. H-work d i s c u s s e d i n t h i s t h e s i s extends these e a r l i e r i n v e s t i g a t i o n s , t o which f u r t h e r r e f e r e n c e w i l l be made i n subsequent  d i s c u s s i o n , t o a study of the oxo r e -  a c t i o n of t h e p e n t a l , 3,4-di-0-acetyl-p_-xylal ( 2 2 ) , and a l s o d e s c r i b e s a f u r t h e r i n v e s t i g a t i o n of the r e a c t i o n of 3,4,6t r i - O - a c e t y l - D - g a l a c t a l (40).  - 32 DISCUSSION A.  Hydroxymethylation o f  Previous  3,4-Di-O-acetyl-D-xylal  work^3,64 h  a  s  demonstrated that the oxo  r e a c t i o n can be a p p l i e d s u c c e s s f u l l y t o the a c e t y l a t e d hexals being  (20 a) and(4o), the major products o f the r e a c t i o n s a c e t y l a t e d a l c o h o l s having one more carbon atom than  the s t a r t i n g m a t e r i a l ; thus the r e a c t i o n s appeared t o f o l l o w the expected course and a hydroxy methyl.'', group was added t o one s i d e of the double bond.  I t could be a n t i c i -  pated that a p p l i c a t i o n of the same r e a c t i o n t o the a c e t y l a t e d p e n t a l s would t h e r e f o r e r e s u l t In the formation of d i - 0 - a c e t y l d e r i v a t i v e s of s i x carbon compounds. j e c t of the work d e s c r i b e d  The ob-  i n t h i s s e c t i o n was t o i n v e s t i -  gate the s t r u c t u r e s of products formed by the r e a c t i o n of 3,4-di-O-acetyl-D-xylal  (22) w i t h carbon monoxide and  hydrogen under hydroxymethylation c o n d i t i o n s , whereby, as a r e s u l t of the a b s o r p t i o n  of 3 moles o f s y n t h e s i s gas p e r  mole of s u b s t r a t e , the a n t i c i p a t e d products a r e a l c o h o l s , r a t h e r than aldehydes -CH=CH-  +  ^2H  g  +  CO,  ->  -CH -CH-CH 0H 2  2  34  3 moles In a l a t e r s e c t i o n (C) experiments w i l l be d e s c r i b e d i n which i t was attempted to terminate the r e a c t i o n a t the aldehyde stage (equation  l),'at  the p o i n t where 1 mole o f  - 33 g l y c a l had absorbed  2 moles of s y n t h e s i s gas.  (i)  Reactants  and R e a c t i o n C o n d i t i o n s  (a)  3,4-Di-O-acetyl-D-xylal  (22)  3,4-Di-O^acetyl-D-xylal i n 1929  (22) was  first  prepared  "~ 65 by Levene and Mori , as an i n t e r m e d i a t e i n the  s y n t h e s i s of 2-deoxy-  -D-xylose,  u s i n g an a d a p t a t i o n of  the o r i g i n a l procedure  ~ of F i s c h e r and  31 Zaeh^ .  of 2 , 3 > 4 - t r i - 0 - a c e t y l - o c - D - x y l o p y r a n o s y l z i n c and 50$ a c e t i c the same procedure  Reduction  bromide (43)  a c i d gave (22) i n 60$ y i e l d .  with  Essentially  has r e c e n t l y been g i v e n as a standard  OAC  ;H,CAC  ->  AcO  CAc  OAc (42)  (22)  ,  35  Br CAc  (43) 66  method f o r the p r e p a r a t i o n of t h i s g l y c a l . Overend and 67 • co-workers ' have p o i n t e d out the n e c e s s i t y of employing low  temperatures  (-5  to -10  ) f o r the c o n v e r s i o n of a c e t o -  bromoaldoses to g l y c a l s , p a r t i c u l a r l y i n the pentose i n order t o minimise the simultaneous products  ((25)  —>  (26)).  series,  formation of s a t u r a t e d  In view of t h i s , the y i e l d of  68 (22) r e p o r t e d by Gakhokidze h i g h as the r e a c t i o n was  (80$  from (43))  performed at room  was  remarkably  temperature.  _ 34 Attempts  t o repeat t h i s p r e p a r a t i o n , however, have r e s u l t e d  o n l y i n the i s o l a t i o n of 2 , 3 , 4 - t r i - O - a c e t y l - D - x y l o s e i n  6Q  ••M'  r a t h e r good y i e l d In  y  ,  t h i s work, the procedure of H e l f e r i c h and co-  45 workers  , i n s l i g h t l y m o d i f i e d form, was  3,4-di-O-acetyl-D-xylal.  used to prepare  Conversion of ( 4 l )  to (22)  was  thus c a r r i e d through without i s o l a t i o n of the i n t e r m e d i a t e compounds (42)  and  (43).  Consistently satisfactory re-  s u l t s were o b t a i n e d u s i n g t h i s procedure p r o v i d i n g the f o l l o w i n g p r e c a u t i o n s were observed; (a)  The e n t i r e p r e p a r a t i o n was  c a r r i e d through as q u i c k l y  as p o s s i b l e , e s p e c i a l l y the f i n a l (b)  stage (43)  The temperature of the z i n c - a c e t i c a c i d  mixture was  not allowed t o exceed  carbon d i o x i d e was  >  (22).  reduction  -10°; a d d i t i o n of s o l i d  e f f e c t i v e i n m a i n t a i n i n g a low  tempera-  t u r e , both d u r i n g the course of the r e a c t i o n and the subsequent (c)  filtration.  Normally, removal of z i n c by f i l t r a t i o n  slow, and as some r i s e i n temperature t h i s stage, undue delay i s l i k e l y I t was  found that f i l t r a t i o n  i s extremely  Is i n e v i t a b l e d u r i n g  t o l e a d to reduced y i e l d s .  c o u l d be g r e a t l y speeded  by  adding C e l i t e t o the r e a c t i o n mixture, and spreading a l a y e r of C e l i t e on the ijjLlter paper b e f o r e f i l t r a t i o n . (c)  •  The crude syrupy product obtained by c h l o r o f o r m ex-  t r a c t i o n of the f i l t r a t e was  d i s t i l l e d without d e l a y .  The  - 35 product thus o b t a i n e d c r y s t a l l i s e d spontaneously,  and  s u f f e r e d no apparent decomposition when s t o r e d f o r s e v e r a l months i n the r e f r i g e r a t o r . T y p i c a l l y , by t h i s procedure, xylal  (22)  was  3>4-di-0-acetyl-D-  obtained from D-xylose  y i e l d of about 6 0 $ . by d i s t i l l a t i o n was  (Hi) i n an  overall  The p u r i t y of the product obtained r e a d i l y demonstrated  by t h i n  layer  chromatography, a c e t y l a t e d g l y c a l s being c o n s i d e r a b l y more mobile on s i l i c a g e l than other components present i n a crude p r e p a r a t i o n . of  i n f r a r e d a b s o r p t i o n of (22)  band at 1640 tion. of  The most c h a r a c t e r i s t i c r e g i o n  cm , -1  i s a sharp, f a i r l y s t r o n g  a s s i g n a b l e t o the C=C  The presence or absence  stretching  vibra-  of t h i s band i s t h e r e f o r e  use i n f o l l o w i n g the course of r e a c t i o n s  involving  a d d i t i o n s t o the double bond. (b)  Reaction Conditions S u i t a b l e c o n d i t i o n s f o r the r e a c t i o n of a c e t y l a t e d  g l y c a l s w i t h carbon monoxide, hydrogen  and d i c o b a l t o c t a -  c a r b o n y l have been w e l l e s t a b l i s h e d as a r e s u l t of p r e v i o u s work^ *. 2  The e a r l y experiments  of Adkins and  s u i t a b l y adapted the oxo r e a c t i o n to a l a b o r a t o r y  Kresk^ scale,  and i n g e n e r a l l i t t l e d e v i a t i o n from these c o n d i t i o n s i s observed i n the experiments  of subsequent  workers.  ever, i n the case of the r e a c t i o n of a c e t y l a t e d  How-  glycals,  - 36 lower temperatures than a r e o f t e n customsfry have been used, o Whereas a t 130  g l y c a l s a r e l a r g e l y converted  by hydroxymethylation  to alcohols  (equation 2 ) , with the m a j o r i t y of  o l e f i n s aldehydes a r e formed predominantly  a t t h i s tempera-  t u r e , and a p p r e c i a b l e a l c o h o l formation i s obtained when the temperature i s r a i s e d by 5©° o r more.  only  The most  r a p i d r e a c t i o n r a t e i s obtained when the r a t i o o f hydrogen  12 to  carbon monoxide i s h i g h  appear t o be the requirement  ; the l i m i t i n g f a c t o r would t h a t the p a r t i a l pressure of  carbon monoxide i s s u f f i c i e n t l y h i g h t o prevent  decomposition  2 of  the c a t a l y s t  .  In p r a c t i c e , 3,4,6-tri-O-acetyl-D-galactai  (40) has been observed  t o r e a c t normally w i t h carbon monoxide  and hydrogen when the i n i t i a l p a r t i a l pressures o f the two gases were 200 and 1700 p . s . i . r e s p e c t i v e l y ^ . F o r the hydroxymethylation  of 3 * 4 - d i - 0 - a c e t y l - D - x y l a l , a carbon  monoxide t o hydrogen r a t i o o f 1^5 was employed, at a t o t a l i n i t i a l pressure o f about 3000 p . s . i . (c) Removal o f C a t a l y s t Wender^® has d e s c r i b e d v a r i o u s methods f o r the removal o f d i c o b a l t o c t a c a r b o n y l c a t a l y s t from oxo r e a c t i o n products.  When the i s o l a t i o n of aldehydes i s not r e q u i r e d ,  the p r e f e r r e d method i s t o r e p l a c e unreacted  s y n t h e s i s gas  w i t h hydrogen under p r e s s u r e , when, on h e a t i n g , the o c t a c a r b o n y l Is decomposed t o m e t a l l i c c o b a l t .  Alternatively,  - 37 d i c o b a l t o c t a c a r b o n y l may  be destroyed by h e a t i n g the  mixture on a steam bath, or shaking with d i l u t e sulphuric?K a c i d s o l u t i o n , u n t i l carbon monoxide i s no l o n g e r e v o l v e d . In  working w i t h the products d e r i v e d from the a c e t y l a t e d  g l y c a l s we have found the most convenient?  method f o r  s e p a r a t i n g r e a c t i o n products from c a t a l y s t M s through P l o r i s i l  by  filtration  (a s y n t h e t i c m a g n e s i a - s i l i c a g e l a b s o r b e n t ) ;  c a t a l y s t i s e l u t e d w i t h petroleum e t h e r , and r e a c t i o n p r o ducts are subsequently e l u t e d w i t h a more p o l a r s o l v e n t , such as a 9*1 (ii) (a)  (v/v) mixture of benzene and e t h a n o l .  F r a c t i o n a t i o n and C h a r a c t e r i s a t i o n of R e a c t i o n Products Chromatographic  S e p a r a t i o n of Products  Evidence that the a n t i c i p a t e d hydroxymethylation the double bond of 3 , 4 - d i - O - a c e t y l - D - x y l a l had o c c u r r e d p r o v i d e d by the i n f r a r e d spectrum  1640  cm"  1  was  of the c a t a l y s t - f r e e  product i s o l a t e d from the r e a c t i o n : at  of  the s t r o n g a b s o r p t i o n  c h a r a c t e r i s t i c of the g l y c a l double bond had  disappeared, and a band of moderate i n t e n s i t y had i n the 3400 c m  -1  r e g i o n (OH stretching;) .  appeared  Thill layer  chromatography showed the presence of a mixture w i t h major components which were not w e l l r e s o l v e d , and  two  indicated  t h a t l i t t l e would be gained i n attempting t o f r a c t i o n a t e the mixture as such. Attempted f r a c t i o n a t i o n by g a s - l i q u i d •i^f71 " p a r t i t i o n chromatography , f o l l o w i n g complete a c e t y l a t i o n  - 38 of f r e e primary h y d r o x y l groups, gave one zone on a column of 20$ S i l i c o n e G.E.S.F. 96 on f i r e b r i c k at 1 9 0 ° ,  which  was  shown to be a mixture of two components by t h i n l a y e r chromatography.  S u c c e s s f u l s e p a r a t i o n of the mixture of products  from the oxo r e a c t i o n was l a t i o n , and chromatography  subsequently e f f e c t e d by deacetyof the r e s u l t i n g mixture of p o l y o l s . •J  F o l l o w i n g d e a c e t y l a t i o n by sodium methoxide i n methan o l ^ , and removal of sodium i o n s w i t h Amberlite IR-120 (H ) 2  +  c a t i o n exchange r e s i n , a syrupy product was  o b t a i n e d , whose  i n f r a r e d spectrum confirmed the complete removal of 0 - a c e t y l groups, and which showed a s t r o n g , broad h y d r o x y l band. P r e l i m i n a r y examination by descending paper  chromatography  r e v e a l e d that the d e a c e t y l a t e d product comprised  mainly  two components, d e t e c t a b l e on s p r a y i n g w i t h p e r l o d a t e 73 >' S c h i f f reagent having an background,  ;  With t h i s spray reagent, compounds  o c - g l y c o l group show as p u r p l e spots on a white by v i r t u e of t h e i r o x i d a t i o n by p e r i o d a t e t o  a d i a l d e h y d e , which r e s t o r e s the c o l o u r o f the S c h i f f r e agent.  A f t e r development f o r about hO hours, u s i n g a s o l -  vent system of w a t e r - s a t u r a t e d 1-butanol c o n t a i n i n g  5$  e t h a n o l , the two major components of the mixture were s u f f i c i e n t l y f a r apart t o enable t h e i r s e p a r a t i o n to be on a p r e p a r a t i v e s c a l e .  effected  A p r e p a r a t i v e s e p a r a t i o n of the  two components of the p o l y o l mixture was a p p l y i n g the m a t e r i a l , i n methanol  c a r r i e d out by  s o l u t i o n , to several  - 39 l a r g e sheets of Whatman's No. 1 paper prepared f o r descending chromatography.  The progress o f the s e p a r a t i o n was f o l l o w e d  by d e t e c t i n g the p o s i t i o n s o f the zones on c o n t r o l chroma tograms which were developed i n the same tank, and was allowed t o continue u n t i l the two components o f the mixture were near the bottom edge o f t h e sheets, thereby a c h i e v i n g maximum s e p a r a t i o n . Three narrow t e s t s t r i p s were cut from ft 73 each l a r g e sheet and sprayed with the z o n e - l o c a t i n g reagent i n order t o ensure t h a t the p o s i t i o n o f each zone was determined a c c u r a t e l y ; the m a t e r i a l so l o s t r e p r e s e n t e d from 5 t o 10$ of each component.  The zones thus  located  were e x h a u s t i v e l y e x t r a c t e d w i t h aqueous methanol;  the two  f r a c t i o n s thus I s o l a t e d , both i n i t i a l l y i n t h e form o f syrups, were found t o be f r e e from contamination by the other on rechromatography  o f a p o r t i o n on paper.  Of the two c h r o m a t o g r a p h i c a l l y pure f r a c t i o n s r e s u l t i n g from the above s e p a r a t i o n , the f a s t e r moving component  w i l l be designated F r a c t i o n I , and the slower,  Fraction I I . (b)  C h a r a c t e r i s a t i o n o f F r a c t i o n s I and I I From an amount o f 400 mg o f the mixture o b t a i n e d on  d e a c e t y l a t i o n o f t h e oxo product, 150 mg o f F r a c t i o n I and 180 mg o f F r a c t i o n I I were r e c o v e r e d from the chromatograms. A l l o w i n g f o r a l o s s o f approximately 10$ o f the m a t e r i a l  _ 40 i n i t i a l l y applied  (as a r e s u l t o f zone l o c a t i o n ) , the com-  bined f r a c t i o n s therefore  r e p r e s e n t e d about 90$ of t h e mix-  ture.  B  (a)  Hp  (a)  n*]2°  l  ( b )  JD  m  ,  p  '  Fraction I  0.47  -13°  102°  Fraction II  0.4l  -44°  —  - i n w a t e r - s a t u r a t e d 1-butanol + 5$ at room temperature  ethanol,  (b)  -ifo|water  F r a c t i o n I , a f t e r c r y s t a l l i s a t i o n t o constant melti n g p o i n t , gave an elemental a n a l y s i s c o r r e s p o n d i n g t o an empirical  formula o f CgH^O^.  Acetylation  of F r a c t i o n I  w i t h a c e t i c a n h y d r i d e - p y r i d i n e gave a syrup which not  could  be c r y s t a l l i s e d , although t h i n l a y e r chromatography  showed t h e homogeneity o f t h e p r o d u c t . characterised |^<xjp - 5 0 ° .  as the p - n i t r o b e n z o y l  This  f r a c t i o n was  d e r i v a t i v e , m.p. 2 1 5 ° ,  The elemental a n a l y s i s of the c r y s t a l l i n e  d e r i v a t i v e corresponded t o the replacement of t h r e e hydrogens o f F r a c t i o n I by three p - n i t r o b e n z o y l  groups.  F r a c t i o n I I r e s i s t e d attempts a t c r y s t a l l i s a t i o n , but  r e a d i l y formed a c r y s t a l l i n e d e r i v a t i v e , m.p. 8 0 - 8 1 ° ,  {^oc] -41°, D  on a c e t y l a t i o n w i t h a c e t i c  anhydride-pyridine.  T h i s d e r i v a t i v e gave an a n a l y s i s c o r r e s p o n d i n g t o C  H-^gOy,  - 41 the t r i - O - a c e t y l d e r i v a t i v e o f F r a c t i o n I I .  I n order t o  o b t a i n F r a c t i o n I I i n a h i g h l y p u r i f i e d form, a p o r t i o n o f the c r y s t a l l i n e a c e t a t e was d e a c e t y l a t e d by t h e a c t i o n o f methanolic  sodium methoxide and t h e product was c a r e f u l l y  i s o l a t e d i n t h e u s u a l way t o g i v e a syrup which d i d not c r y s t a l l i s e , but which a n a l y s e d s a t i s f a c t o r i l y f o r CgH 04« 12  (iii) (a)  I d e n t i f i c a t i o n o f F r a c t i o n s I and I I P e r i o d a t e Consumption I n f o r m a t i o n on t h e s t r u c t u r e o f a carbohydrate can 74  be gained from a study o f i t s r e a c t i o n w i t h p e r i o d a t e i o n ' . The c h i e f a n a l y t i c a l a p p l i c a t i o n of t h i s r e a c t i o n i s i n the d e t e r m i n a t i o n o f the number o f adjacent h y d r o x y l groups i n the molecule,  as each  ex.-glycol group consumes one  molecular p r o p o r t i o n o f p e r i o d a t e , the r e s u l t i n g fragments being formaldehyde, formic a c i d or a s u b s t i t u t e d aldehyde a c c o r d i n g t o the l o c a t i o n of t h e p a r t i c u l a r group  undergoing  oxidation.  CHGH  HCHO + HCOOH + CHO  R  R  CHOH  Other groups such as and  cx-amino-alcohols  IO4  oc-hydroxyaldehydes,  36  oc-hydroxyketones  a r e a l s o c l e a v e d by p e r i o d a t e .  - 42 V a r i o u s methods are i n common use f o r f o l l o w i n g the "]'  75 " r e a c t i o n of v i c i n a l h y d r o x y l groups w i t h p e r i o d a t e i o n u s u a l l y i n v o l v i n g t i t r i m e t r i c procedures and  ,  r e q u i r i n g the  d e s t r u c t i o n of a p p r e c i a b l e amounts of m a t e r i a l .  The  spectro-  76  photometric 8  method of Dixon and  Lipkin  , r e q u i r i n g only  1  6  10"  to 10~  mole of sample, appeared t o be eminently  a b l e f o r determining  the number of v i c i n a l h y d r o x y l  suit-  groups  i n F r a c t i o n s I and I I , l i m i t e d amounts of which were a v a i l able. may  These workers found t h a t consumption of  be f o l l o w e d s p e c t r o p h o t o m e t r i c a l l y at 223  periodate ttyx, at which  77 wavelength i t s a b s o r p t i o n i s at a maximum  .  No  inaccuracies  were i n t r o d u c e d by the r e l a t i v e l y s m a l l a b s o r p t i o n of i o d a t e i o n i n t h i s r e g i o n , nor by a b s o r p t i o n of unconjugated c a r F o l l o wlii n g t h i s procedure, the decrease i n absorbance bonyl compounds formed d u r i n g the r e a c t i o n . at 223 rn/A. of a s o l u t i o n of F r a c t i o n I (0.439 x 10 the b a s i s o f a molecular  weight of 200)  c o n t a i n i n g an  M  on  excess  -4 (0.942 x 10  of sodium p e r i o d a t e  p e r i o d of s e v e r a l hours.  M)  was  Each r e a d i n g  Model DU Spectrophotometer was  measured over a  (A) on the Beckman  accompanied by a r e a d i n g  4 (B) of a c o n t r o l s o l u t i o n 0.942 x 10  M with respect  to  -4 p e r i o d a t e i o n , and a l s o of a s o l u t i o n c o n t a i n i n g 0.439 x 10 M i n absorbance due to consumption of p e r i o d a t e i o n by F r a c t i o n of F r a c t i o n I ( C ) . Thus (B+C)-A was a measure of the decrease I . Then (^+ )," the f r a c t i o n of the known amount of C, o c  A  w  a  s  - 43 added p e r i o d a t e which was any time, where C  Q  was  -  consumed by the carbohydrate  at  the measured absorbance of the p e r i o -  date s o l u t i o n at zero time ( t h i s changes s l o w l y w i t h time  77 because of v a r i a t i o n s i n pH,  temperature  x  ).  I t was  found  t h a t A reached a constant value e q u i v a l e n t to the consumpt i o n of 0 . 9 0 . m o l e of p e r i o d a t e i o n per mole of F r a c t i o n I . A s i m i l a r s e r i e s of measurements with F r a c t i o n I I gave a  1  •i value of 0.95/'moles of p e r i o d a t e per mole o f s u b s t r a t e . With due allowance  f o r the micro  s c a l e of these  these r e s u l t s t h e r e f o r e showed the presence  analyses,  of two  vicinal  h y d r o x y l groups i n each compound. (b) S t r u c t u r e s of F r a c t i o n s I and I I Thus f f r , the Information o b t a i n e d on F r a c t i o n s I and I I i n d i c a t e d that both c o n t a i n e d three h y d r o x y l groups/ two  of which were v l c l n a l l y s i t u a t e d .  On t h i s  evidence,  and from a c o n s i d e r a t i o n of the l i k e l y mode of a d d i t i o n of carbon monoxide and hydrogen to 3 , 4 - d i - O - a c e t y l - D - x y l a l it  c o u l d be assumed t h a t the r e a c t i o n had f o l l o w e d the  (22) ex-  pected course, and a hydroxymethyl group had added to the double bond.  On t h i s b a s i s , f o u r Isomers (44)  were p o s s i b l e , a l l of which c o n t a i n two  vicinal  to  (47)  secondary  - 44 h y d r o x y l g r o u p s - i n a d d i t i o n t o one primary h y d r o x y l group, and t h e r e f o r e c o u l d not he d i s t i n g u i s h e d on the a v a i l a b l e evidence.  S t r u c t u r e s (44)  and  a d d i t i o n of a hydroxymethyl  (45),  r e s u l t i n g from the  group at C - l of the g l y c a l ,  are l,5-anhydro-4-deoxy-hexitols, d i f f e r i n g i n the c o n f i g u r a t i o n o f carbon 5» i n accordance w i t h accepted nomenclature^®, (44)  and  (45) are p r e f e r a b l y drawn i n the f o l l o w i n g  OH  OH  (44)  (45)  Hydroxymethylation a t C-2  of the g l y c a l would g i v e e i t h e r  of the branched-chain isomers  (46)  and  (47), which are  l,5-anhydro-2-deoxy-2-hydroxymethyl-pentitols, c o n f i g u r a t i o n of the s i d e c h a i n a t I t was  way  differing in  C-2.  p o s s i b l e t o d i s t i n g u i s h between the s t r a i g h t  c h a i n and branched  c h a i n s t r u c t u r e s merely from a c o n s i d e r a -  t i o n of the resonance p o s i t i o n s and r e l a t i v e i n t e n s i t i e s of the proton s i g n a l s observed i n the n u c l e a r magnetic  resonance  s p e c t r a o f F r a c t i o n s I and I I , measured i n deuterium oxide solution.  I n t h i s s o l v e n t , h y d r o x y l i c protons are r a p i d l y  exchanged and are r e s o l v e d i n t o one sharp H-O-D  s i g n a l ; the  - 45 spectrum (44)  i s thereby s i m p l i f i e d .  Consideration of structures  t o (47) shows that i n both s t r a i g h t c h a i n and branched  c h a i n isomers a r e present (a) methylene protons oxygen, C-CHg-O-, and (b) a methine proton function, and  o t t o an  OC t o an oxygen  ' I n ^he - s t r a i g h t c h a i n isomers  (44)  ( 4 5 ) , a methylene group i s a l s o present which i s f l a n k e d  by two carbon atoms ; (c) C-CH -C, whereas i n the branched 2  c h a i n isomers  (46) and (47) a t e r t i a r y hydrogen, r a t h e r C  than a methylene group, i s p r e s e n t ; (d) G-6H-C. fundamental  t o n u c l e a r magnetic  the resonance  resonance  p o s i t i o n , o r chemical s h i f t ,  It is  spectroscopy that of a proton  depends upon i t s p r e c i s e chemical environment.  Ample evidence  i s a v a i l a b l e t o i n d i c a t e w i t h c e r t a i n t y that protons o f types (a) and (b) above w i l l resonate a t a lower magnetic than w i l l type  field  (e) and (d) p r o t o n s , because t h e i n d u c t i v e  e f f e c t o f the adjacent oxygen atom w i l l reduce the e l e c t r o n d e n s i t y around  these p r o t o n s .  Jackman^^ t a b u l a t e s t y p i c a l  v a l u e s f o r methylene and methine protons w i t h an f u n c t i o n as l y i n g between 6.15 and 6.6© T ppm),  shift  ( 8 = 3.85-3.40  whereas t h e c o r r e s p o n d i n g protons i n s a t u r a t e d hydro-  carbons resonate around from  oc-oxygen  8.5 t  ( 1 . 5 pptn), w i t h d e s h i e l d l n g  - s u b s t i t u e n t s r e s u l t i n g i n a c o m p a r a t i v e l y minor t o lower  field.  Consequently,  i n DgO s o l u t i o n , i t was a n t i c i p a t e d  that  the n o n - h y d r o x y l i c hydrogens o f t h e s t r a i g h t c h a i n isomers (44)  and (45) would e x h i b i t two types o f s i g n a l s :  a group  - 46 at  lower f i e l d of r e l a t i v e i n t e n s i t y 7,  type  (a) and  (c).  of  corresponding to  (b) protons, and a h i g h e r f i e l d group of r e l a -  t i v e i n t e n s i t y 2,  and  -  corresponding to %f\e two methylene protons,  On the other hand, w i t h the branched (47)  J46)  c h a i n isomers  the lower f i e l d . g r o u p would have a r e l a t i v e  intensity  8 , whereas the s i n g l e t e r t i a r y hydrogen (d) would resonate  at h i g h e r f i e l d w i t h an i n t e n s i t y of 1.  The observed n.m.r.  spectra of F r a c t i o n s I and I I both showed the a n t i c i p a t e d s e p a r a t i o n of s i g n a l s i n t o lower and h i g h e r f i e l d peak at 8 = #.73  ( i n a d d i t i o n to the s i n g l e H-O-D  groups, ppm).  In  both cases the area enclosed by the lower f i e l d group of signals at  ( S = 2 . 9 - 4 . 2 .ppm)  higher f i e l d  (S =  was  3.5  times t h a t of the group  1 . 1 - 2 . 2 ppm).  T h i s c l e a r l y demonstrated  t h a t both F r a c t i o n s I and I I were i s o m e r i c 1 , 5 - a n h y d r o - 4 d e o x y - h e x i t o l s ( s t r u c t u r e s (44)  (45)).  and  Additional i n -  f o r m a t i o n r e g a r d i n g the s t e r e o c h e m i s t r y of these compounds can be d e r i v e d from a c o n s i d e r a t i o n of the m u l t i p l i c i t i e s  of  the h i g h e r f i e l d s i g n a l s ? t h i s aspect i s d i s c u s s e d i n more detail  later. F u r t h e r c o n f i r m a t i o n t h a t F r a c t i o n s I and I I were  isomeric l,5-anhydro-4-deoxy-hexitols ing  argument.  was  based on the f o l l o w -  P e r i o d a t e cleavage of the  i n a l l f o u r s t r u c t u r e s (44)  -  (47)  oc - g l y c o l group  .•  would f u r n i s h a dialdehyde  which on r e d u c t i o n would g i v e a s t r u c t u r e having t h r e e mary h y d r o x y l groups and an e t h e r l i n k a g e .  pri-  However, whereas  from and  (44) (49)  and  (45)  a pair o f  enantiomeric t r i b l  (48)  ethers  would b e o b t a i n e d , e a c h having one c e n t r e of asym-  metry (-fc), t h e c h a i n isomers,  same r e a c t i o n s a p p l i e d to e i t h e r (46)  or  tically-inactive triol  . (47), would r e s u l t ether  (50)  i n the same op-  being formed.  onpn  CrjpH  KC-O-CH^CI-ph!  HOChp-jjO-C-H  ChjpH  .ChjpH  (48)  or  OH  (49)  9 4P (46)  branched  (45)  H  CH-a-^-0-CH CH OH Chj,OH  (4?)  2  2  (50)  Both F r a c t i o n s I a n d I I w e r e s e p a r a t e l y t r e a t e d , i n t h i s way,  a c c o r d i n g t o a p r o c e d u r e s i m i l a r to t h a t d e s c r i b e d  80 by von R u d l o f f a n d co-workers was  oxidised w i t h a 50$ e x c e s s  .  A sample of each  polyol  o f periodic acid u n t i l  o p t i c a l r o t a t i o n s of t h e s o l u t i o n s were c o n s t a n t .  the  After  n e u t r a l i s i n g w i t h b a r i u m carbonate the s o l u t i o n s were t r e a t e d w i t h an aqueous s o l u t i o n of s o d i u m b o r o h y d r i d e ; c a t i o n s were removed w i t h -Amberlite- IR-120(H"*) r e s i n , and borate i o n  was  - 48 v o l a t a l i s e d as the methyl was  ester  81  The product In both cases  a syrup. The t r i o l ether o b t a i n e d from F r a c t i o n I had  and t h a t from F r a c t i o n I I had [p^-p +17 . 0  i d e n t i c a l n.m.r. s p e c t r a ,  8 -  1.5  -19°,  Both products had  measured i n deuterium oxide s o l u -  t i o n , w i t h a group of s i g n a l s 8 = 3.5 f i e l d group at  D  - 2.0  ppm,  - 3*9  ppm,  and a h i g h e r  the r e l a t i v e areas of the  two groups being i n the r a t i o of 9 2 .  Hence the products  :  r e s u l t i n g from the p e r i o d a t e o x i d a t i o n and sodium borohydride r e d u c t i o n of the two p o l y o l s were c l e a r l y the enantiomeric D-  (48)  and L- (49)  forms of  2-deoxy-3-0-(2-hydroxyethyl)-  glycero-tetritol. I t was  noted t h a t , i n the course of an i n v e s t i g a t i o n  of the products r e s u l t i n g from the h y d r o g e n o l y s i s of methyl Oc-D-glucopyranoside  (51)  under c o n d i t i o n s of h i g h tempera-  t u r e and p r e s s u r e , and i n the presence of a copper c a t a l y s t , von R u d l o f f and co-workers® to s e v e r a l other p r o d u c t s , a tetrahydropyran (52); it  0  chromite  had i s o l a t e d , i n a d d i t i o n  2-hydr6xymethyl-4,5-dihydroxy-  (considered as a carbohydrate, (52)  1,5 -a nhydro -4j|deoxy -hexi t o l )  •  is a •  CH 0H 2  HO  ,OH  (51)  +  6CH, Ohl  CKpH  other products 40  - 4  9  -  The m o l e c u l a r s t r u c t u r e o f (52) (which l a t e r to  be a mixture o f stereoisomers  proved  ) was demonstrated by  p e r i o d a t e o x i d a t i o n t o a dialdehyde which was then  reduced  w i t h sodium borohydride t o an open c h a i n t r i o l e t h e r ( 5 3 ) , c h a r a c t e r i s e d as t h e t r i a c e t a t e . e t h e r was proved i n two ways:  The s t r u c t u r e o f t h e t r i o l  (a) e t h y l i o d o a c e t a t e was  condensed w i t h d i e t h y l L-twaiate i n t h e presence o f sodium, and the r e s u l t i n g t r i e s t e r  (54) was reduced w i t h l i t h i u m  aluminum h y d r i d e  COOEt ICH  .COOEt  I  Na  -+ CH„  2  COOEt  |_ 2 HO-C-H  I  /x (b)  cleavage o f the t r i o l  2  I  LiAlHh  CH  >  2  I  0  CH-0-CH .COOEt  CH-0-CHo.CH^OH  COOEt  CH 0H  (54)  (53)  I  0  I  COOEt  CH <3H  I  2  2  2  ether w i t h boron  i n a c e t i c anhydride and subsequent  2  83  trichloride  d e a c e t y l a t i o n gave ethane-  d i o l and 1 , 2 , 4 - b u t a n e t r i o l  CH20H  I  CH^OH  o  CH^  BC1.  I  2  H0CHiCH 0H  2^ 2 o  CH-0-CH .CH OH  CHOH  CH OH  CH OH  I  p  (53)  2  42  - 50 The product  (52) from the h y d r o g e n o l y s i s o f  (51)  Op  was f u r t h e r i n v e s t i g a t e d by G o r i n  , who f r a c t i o n a t e d the  m a t e r i a l by c e l l u l o s e column chromatography Into two i s o meric  l,5-anhydro-4-deoxy-hexitols.  and borohydride  Periodate oxidation  r e d u c t i o n o f both components a f f o r d e d the  same t r i o l e t h e r , which demonstrated t h a t the c o n f i g u r a t i o n of  the hydroxymethyl group was the same i n each case, and  t h e r e f o r e the two compounds d i f f e r e d i n the c o n f i g u r a t i o n of  the v i c i n a l h y d r o x y l s on the r i n g .  The t r i o l  ethers  obtained by G o r i n were l e v o r o t a t o r y ( [°<GD - 2 0 ° ,  -l6°),  and were c h a r a c t e r i z e d as the t r i s - p - n i t r o b e n z o a t e s , m e l t i n g p o i n t s 103-104°, 9 8 - 1 0 2 ° , s p e c i f i c r o t a t i o n s - 2 6 ° , The  enantiomeric  triol  -22°.  ethers obtained from F r a c t i o n s  I and I I , which f o r the sake o f convenience  w i l l be designated  as compounds I I I and IV r e s p e c t i v e l y , were converted t o p - n i t r o b e n z o y l d e r i v a t i v e s a c c o r d i n g t o the procedure of ftp  Gorin° .  The l e v o r o t a t o r y t r i o l  ether I I I from F r a c t i o n I  gave a c r y s t a l l i n e d e r i v a t i v e m.p. 1 0 2 - 1 0 3 ° , 0*0 D - 2 8 ° , which did  not depress  the m e l t i n g p o i n t of Gorin's  tris-p-nitro-  oji  benzoate II,  , and the d e x t r o r o t a t o r y t r i o l e t h e r IV, from Fraction  f u r n i s h e d the enantiomeric  d e r i v a t i v e , m.p.  w i t h an equal and opposite s p e c i f i c r o t a t i o n . ftO work o f von R u d l o f f and co-workers  102-103°, As the previous  had c l e a r l y demonstrated  the p o s i t i o n s o f attachment o f the hydroxymethyl group and the two secondary  h y d r o x y l groups t o the t e t r a h y d r o p y r a n  - 51 r i n g of ( 5 2 ) ,  -  these r e s u l t s p r o v i d e d a d d i t i o n a l and  con-  c l u s i v e proof t h a t F r a c t i o n s I and I I were i s o m e r i c  1,5-  anhydro-4-deoxy-hexitols. One  i m p l i c a t i o n of the demonstrated  between the two methyl  relationship  i s o m e r i c anhydrodeoxyhexitols d e r i v e d from  cx-D glucopyranoside r  (51)  and F r a c t i o n I was  assuming no i n v e r s i o n of c o n f i g u r a t i o n o c c u r r e d at C-5 the g l y c o p y r a n o s i d e r i n g of (51)  that, of •  d u r i n g the h y d r o g e n o l y s i s  r e a c t i o n , then F r a c t i o n I must have the D c o n f i g u r a t i o n at C-5  (44),  and consequently F r a c t i o n I I must have the L-  c o n f i g u r a t i o n at t h i s c e n t r e ( 4 5 ) . t i o n was  However, such an assump-  not c o n s i d e r e d s u f f i c i e n t l y j u s t i f i a b l e without  f u r t h e r c o n f i r m a t i o n , f o r two  reasons:  80 1.  The h y d r o g e n o l y s i s r e a c t i o n of von R u d l o f f and  was  c a r r i e d out under extremely vigorous c o n d i t i o n s , and i n  co-workers  g e n e r a l i t has been found t h a t these r e a c t i o n s are accompanied  8s 86 by c o n s i d e r a b l e c o n f i g u r a t i o n a l changes 2.  Assuming the secondary h y d r o x y l groups  of F r a c t i o n s I  and I I were unchanged i n c o n f i g u r a t i o n as a r e s u l t of the oxo r e a c t i o n , then on the b a s i s of the evidence d e s c r i b e d above, of the two p o s s i b l e l , 5 - a n h y d r o - 4 - d e o x y - h e x i t o l s , one of the two f r a c t i o n s must be 1,5-anhydro-4-deoxy-D-arablnohexitol  (44),  Isomer (45).  and the other must be the c o r r e s p o n d i n g L - x y l b Both the anhydrodeoxyhexitols I s o l a t e d by  iorln  - 52  (44)  =  -  H-C-OH H O - i - H .(J> (45) =  Q  HO-i-H  H-C ^ ihiOH'  were assumed to be of the D - s e r i e s as they were d e r i v e d from a D-glucopyranoside  (51),  and on the b a s i s of c e r t a i n  evidence, which w i l l be d i s c u s s e d i n more d e t a i l below, were assigned the D-arablno-(44) and D-lyxo-(6o) c o n f i g u r a t i o n s . However, the p r o p e r t i e s of the isomer which was to have the D - a r a b i n o - c o n f i g u r a t i o n (44)  considered  d i d not resemble  those of e i t h e r F r a c t i o n I or F r a c t i o n I I . ( i v ) C o n f i g u r a t i o n s of F r a c t i o n s I and (a) Stereochemistry The  at  II  C-5  s t e r e o c h e m i s t r y at C-5  d e o x y - h e x i t o l s I and I I was  of the 1 , 5 - a n h y d r o - 4 -  e s t a b l i s h e d w i t h c e r t a i n t y once  i t was  known which of the enantiomeric  IV was  2-deoxy-3-0-(2-hydroxyethyl)-D-glycero-tetritol  and which was  the L-isomer (49).  t r i o l ethers I I I and  Attempts were made to  o b t a i n one of the o p t i c a l l y - p u r e enantiomers by an r o u t e J t h i s was  (48),  unequivocal  r e a l i s e d by the p r e p a r a t i o n of the L-isomer  (49)  from a s t r u c t u r e of known s t e r e o c h e m i s t r y , 1,4-anhydro-  5-deoxy-B-arabino-hexitol  (59),  obtained from the known com-  pound 3,6-anhydro-2-deoxy-B-lyxo-hexose (58)  on r e d u c t i o n  The anhydrodeoxy-sugar (58)  w i t h sodium borjfehydride.  o b t a i n e d by the procedure o f P o s t e r and co-workers "^ 0  methyl 2-deoxy-oc-B-galactopyranoside was  prepared from B - g a l a c t a l  CH OH  (55),  HO  from  which i n t u r n .  (19).  CHpTs  CHpH  2  was  HO  HO J  Ov  OH  OH  OMe (19)  OMe  (56)  (55)  CH^OH  GHO  (49)  OMe (57) (58)  (59) B-galactal B - g a l a c t a l (4G)  (19)  was  o b t a i n e d from  3,4,6-tri-O-acetyl-  on d e a c e t y l a t l o n w i t h methanolic  sodium metho-  88 xide  J t r a n s e s t e r i f i c a t i o n of (40)(and o t h e r a c e t y l a t e d  89,66  N  glycals  ) under these c o n d i t i o n s i s u n u s u a l l y slow, t a k i n g  2 days f o r completion.  B-galactal crystallised readily  from  - 54 the r e s i d u e remaining a f t e r n e u t r a l i s a t i o n and e v a p o r a t i o n of s o l v e n t , upon e x t r a c t i o n w i t h e t h y l a c e t a t e . P r e p a r a t i o n s of methyl 2-debxy-D-galaetopyranoside (55)  have been r e p o r t e d by Tamm and R e i c h s t e i n  Overend and co-workers was  first  and by  ; i n each case D - g a l a c t a l ( l 4 )  c o n v e r t e d t o 2-deoxy-D-galactose by the a d d i t i o n  of water a c r o s s the double bond i n d i l u t e s u l p h u r i c s o l u t i o n , and the sugar was  then methylated i n the presence  of hydrogen c h l o r i d e , the more s t a b l e being i s o l a t e d i n c r y s t a l l i n e form.  cx-glycoside The l a t t e r  a l s o observed the d i r e c t f o r m a t i o n of (55) was  t r e a t e d w i t h 3.3$  acid  (55)  workers  when D - g a l a c t a l  methanollc hydrogen chloride'} and 4  91 F o s t e r , Overend and Stacey  o b t a i n e d the  oc-methyl  glyco-  s i d e on a q u a l i t a t i v e s c a l e when a s o l u t i o n of D - g a l a c t a l i n 0.4$ methanollc hydrogen c h l o r i d e was  a l l o w e d to r e a c h  r o t a t i o n a l e q u i l i b r i u m over 43 minutes.  The one step con-  v e r s i o n of D - g a l a c t a l t o methyl 2-deoxy-oc-D-galactopyranoslde was  used on a p r e p a r a t i v e s c a l e i n t h i s work.  The change  i n o p t i c a l r o t a t i o n of a s o l u t i o n of D - g a l a c t a l methanol c o n t a i n i n g 0 . 3 $ hydrogen c h l o r i d e was  (19) i n followed,  and found t o be constant a f t e r about 50 minutes. was  A syrup  i s o l a t e d from t h i s r e a c t i o n which c r y s t a l l i s e d  readily  on adding a s m a l l volume of acetone; the product was f i e d as (55)  from i t s m e l t i n g p o i n t of 112-114°,  and c o - w o r k e r s ^  2  found 112-113°)•  identi-  (Overend  - 55  -  The p r e p a r a t i o n of 3>6-anhydro-2-deoxy-D-lyxo-hexose (58)  from  (55)  co-workers^ ; 7  was  c a r r i e d out by the method of F o s t e r and  these workers a p p l i e d the known procedure  of Haworth and co-workers^  2  f o r the p r e p a r a t i o n of 3,6-anhydro-  sugars, i n v o l v i n g a l k a l i n e treatment of the 6 - Q - p - t o l y s u l p h o n y l d e r i v a t i v e s of the methyl g l y c o s i d e s , w i t h f o r m a t i o n of the corresponding methyl 3 ,.6-a n h y d r o - g l y c o s i d e s . of (55)  Thus r e a c t i o n  w i t h 1 molar e q u i v a l e n t of p - t o l u e n e s u l p h o n y l c h l o r i d e  under c o n d i t i o n s f a v o u r a b l e f o r unimolar s u l p h o n y l a t i o n ^ gave 0  the syrupy 6 - 0 - p - t o l y l s u l p h o n y l d e r i v a t i v e treatment w i t h base was  converted to methyl  (56),  which on  3,6-anhydro-2-  deoxy- cx-D-galactopyranoside (57)*  m.p.  ( F o s t e r and co-workers^  80°, [pc]15 ^ 9 8 ° ) .  7  g i v e m.p.  76-77°,  2  proof of the c o n f i g u r a t i o n of the t r i o l e t h e r (49)  5 + 94  0  As  ultimately  obtained from l , 4 - a n h y d r o - 5 - d e o x y - D - a r a b i n o - h e x i t o l  (59)  e s s e n t i a l l y depends upon a knowledge of the c o n f i g u r a t i o n at C-3  the anhydro-deoxy-galactoside  (57),  i t i s necessary  t o c o n s i d e r the evidence f o r the s t r u c t u r e of t h i s compound: (a)  (57)  was  toljsulphonyl (b)  c h a r a c t e r i s e d as the c r y s t a l l i n e 4-0-pderivative^ . 7  When the syrupy 6 - 0 - p - t o l y l s u l p h o n y l d e r i v a t i v e  from which (57)  was  prepared, was  (56),  heated w i t h sodium i o d i d e  i n acetone s o l u t i o n , an e q u i v a l e n t amount of sodium ptoluenesulphonate was group of (56) (c)  o b t a i n e d , evidence t h a t the t o s y l o x y  i s at the primary  (C-6)  position^.  The mechanism of f o r m a t i o n of anhydro-sugars  i n basic  medium i s w e l l e s t a b l i s h e d , and has been reviewed by ?eaty  .  3,6-Anhydro-sugars are o f the hydrofuran'ol type, In which the anhydro-ring i s 5-membered; both t h i s type and the w e l l known ethylene oxide prepared by treatment  (3 membered) anhydrides a r e o f t e n r  o f a t o s y l d e r i v a t i v e w i t h base.  r e a c t i o n i n v o l v e s an i n t r a m o l e c u l a r a carbonium  The  exchange o f anions a t  i o n , whereby a t o s y l o x y group i s r e p l a c e d by  a n i o n i c oxygen, and i s most c l e a r l y i l l u s t r a t e d w i t h r e f e r ence t o the ethylene oxide type o f anhydride.  Thus anhydride  44  f o r m a t i o n i n v o l v e s i n v e r s i o n o f c o n f i g u r a t i o n a t the carbon atdm b e a r i n g the p o t e n t i a l l e a v i n g group (which may a l s o be halogen or other m i n e r a l a c i d e s t e r group), but no i n v e r s i o n o f c o n f i g u r a t i o n occurs a t the h y d r o x y l i c  carbon.  f o l l o w s t h a t the d i s p l a c i n g i o n must have a t r a n s ment w i t h r e s p e c t r i n g can form.  It  arrange-  t o the l e a v i n g group b e f o r e an anhydride  The same p r i n c i p l e holds i n the f o r m a t i o n  of 3,6-anhydrides  as a r e s u l t of replacement  group at C-6 by n u c l e o p h i l i c oxygen a t C - 3 .  of a t o s y l o x y As C-6 Is not  asymmetric no i n v e r s i o n of c o n f i g u r a t i o n i s apparent; however,  .  - 57 -  the f o r m a t i o n s t i l l r e q u i r e s a t r a n s d i s p o s i t i o n of the e n t e r i n g and l e a v i n g groups. h y d r o x y l group a t C-3  For s t e r i c reasons the f r e e  must be on the same s i d e of the sugar  r i n g as the s i d e c h a i n , C - 6 .  C l e a r l y , t h e r e f o r e , formation  of >3,6-anhydro-sugars under these c o n d i t i o n s r e s u l t s i n no  c o n f i g u r a t i o n 1 i n v e r s i o n at C - 3 , (58)  and  (59),  o b t a i n e d from  on sodium borohydride r e d u c t i o n , must have the re-  c o n f i g u r a t i o n at  C-4.  3,6-Anhydro-2-deoxy-D-lyxo-hexose (58). was on treatment of the anhydrodeoxygalactoside a c i d at room temperature, as a syrup,  r I  o  |OcJ +24 (58)  t? 3 + 2 5 <  0  D  with d i l u t e (reported  8 7  ).  u  D  sugar  (57)  obtained,  Fost er and co-workers  e x i s t s i n the aldehydo-form,  note that the readily  anhydro-  restoring  the c o l o u r t o S c h i f f reagent, and a c a r b o n y l band a t about 1715  cm"  1  product.  was  observed i n the i n f r a r e d spectrum of the  In t h i s r e s p e c t (58)  d i f f e r s from the corresponding  d e r i v a t i v e s of D-glucose and D-mannose, which e x i s t i n thje furanose form, an arrangement of two e l s - f u s e d 5-membered .  - 58 r i n g s being i n a l e s s - s t r a i n e d s t a t e than a b r i d g e a c r o s s a pyranose r i n g .  Such an arrangement i s not  p o s s i b l e i n 3,6-anhydro-D-galactose (58),  because  3,6-anhydride  and I t s 2 - d e o x y - d e r i v a t i v e  of the o r i e n t a t i o n of the h y d r o x y l group at  C-4. Reduction of (58)  w i t h sodium borohydride gave (59),  anhydro-5-deoxy-D-arablno-hexitol  as evidenced by t h e ,  disappearance of carbonyl. a b s o r p t i o n i n the i n f r a r e d . anhydrodeoxyhexitol  (59),  1,4-  The  which does not appear to have been  25 r e p o r t e d p r e v i o u s l y , had was  [Py £  +21°,  and was  a syrup.  It  c h a r a c t e r i s e d as the t r l s - p - n l t r o b e n z o y l d e r i v a t i v e ,  CP'GQ  (59)  m.p.  159-l60 ,  G.1M  p e r i o d i c a c i d , under c o n d i t i o n s s i m i l a r t o those employed  2  O  -96°.  was  o x i d i s e d w i t h excess  f o r the cleavage of F r a c t i o n s I and I I .  By comparison  these previous r e a c t i o n s , the o x i d a t i o n of (59) as would be a n t i c i p a t e d f o r a'trans  slow,'  ( X - g l y c o l group-on a  ~  •74 5-membered r i n g  was  with  .  Sodium borohydride r e d u c t i o n of the r e -  s u l t i n g .dialdehyde then gave L-glycero-tetritol  2-deoxy-3-0~(2-hydroxyethyl)-  (49) ; t h i s had M  t r i s - p - n i t r o b e n z o a t e , m.p.  101-102°,  m e l t i n g p o i n t was., undepressed  D  + 1 7 ° , , and formed a C^clp+27°,  whose  on admixture w i t h the p-  n i t r o b e n z o a t e of the t r i o l e t h e r IV obtained from F r a c t i o n I I . Thus, F r a c t i o n I I must have the L - c o n f i g u r a t i o n at C-5,  and F r a c t i o n I , which on cleavage and r e d u c t i o n a f f o r d e d  the enantiomeric at  C-5.  t r i o l e t h e r I I I , must have the.©-configuration  These r e s u l t s confirmed Gorin's assumption  no i n v e r s i o n o c c u r r e d a t . C - 5 of methyl (51)  82  that  Oc-D-glucopyranoside  d u r i n g the course of the h y d r o g e n o l y s i s of t h i s  compound® , 0  and t h e r e f o r e both p o l y o l s i s o l a t e d from t h i s r e a c t i o n were of (b)  the D - s e r i e s . C o n f i g u r a t i o n s of Secondary Hydroxyls An element of disagreement  of F r a c t i o n s I and I I  with Gorin's r e s u l t s  prevented a completely unequivocal assignment of the arablno-(44)  D-  and L - x y l o - ( 4 5 ) c o n f i g u r a t i o n s to the two  h y d r o d e o x y h e x i t o l s , F r a c t i o n s I and I I r e s p e c t i v e l y . . found that h i s two p o l y o l s , which f o r the sake of  still  anGorin®  2  convenience  w i l l be designated as X and Y, consumed l e a d t e t r a a c e t a t e at  d i s t i n c t l y d i f f e r e n t r a t e s , X being o x i d i s e d f o u r times  f a s t e r than Y i n the i n i t i a l  stages.  As both p o l y o l s were  otherwise s t r u c t u r a l l y s i m i l a r , t h i s was t h a t X contained a c i s , and Y a t r a n s Assuming t h a t the c o n f i g u r a t i o n at C-5  taken as  evidence^  o c - g l y c o l group. was  D i n both  cases  (an assumption j u s t i f i e d by our r e s u l t s ) , a t o t a l of f o u r p o s s i b l e isomers, two  c i s and two  D-lyxo  D-ribo  (60)  (61)  t r a n s , was  then c o n s i d e r e d .  D-arabino (44)  D-xylo  (62)  - 60  F o r p o l y o l s X and Y, G o r l n found s p e c i f i c r o t a t i o n s of and 4 1 9 °  respectively.  -50°  These values were compared w i t h  those c a l c u l a t e d by a p p l i c a t i o n of the p r i n c i p l e of o p t i c a l s u p e r p o s i t i o n , f i r s t p o s t u l a t e d by van't Hoff and a p p l i e d t o carbohydrates by Hudson ^ i 0  n  later  the form of h i s  I s o r o t a t i o n Rules.  F o r each of the f o u r p o s s i b l e i s o m e r i c  anhydrodeoxyhexitols  (44),  the molecular r o t a t i o n was  (60),  (6l)  (62),  and  a value f o r  d e r i v e d by r e f e r e n c e to a p a i r  of s t r u c t u r e s - o f known molecular r o t a t i o n s , whose i n d i v i d u a l asymmetric  c e n t r e s " c a n c e l l e d out" except f o r those which  were a l s o present i n the a n h y d r o d e o x y h e x i t o l .  T h i s i s best  i l l u s t r a t e d by two examples, s e l e c t e d from the s i x t a b u l a t e d D-arabino-(44)  by G o r l n , which p e r t a i n t o the D - l y x o - ( 6 o ) and isomers.  (+a)  (-b)  HO~(>H  (-c)  HO-(U-t  (-e)  H-C-  0.  '  CH^OH (60)  (-a) 3  ^  (-b)  HO-C-H  (-cj  HO-C-H  (-d)  HO-£--H  (-e)  H-Q-  H  O  C  ° y ^  (-b)  HO-C-H ^  (-c)  HO-C-H  M) (-e)  CH OH  H,OH  2  (64)  (63)  Let the t h r e e i n d i v i d u a l c e n t r e s of asymmetry i n 1,5-anhydro-4-deoxy-D-lyxo-hex!t o l  (60)$  at carbon's 2 ,  3 and  S-61  -  5, "be a s s i g n e d i n d i v i d u a l c o n t r i b u t i o n s  t o the t o t a l mole-  c u l a r r o t a t i o n o f -b, -c and -e. The corresponding c o n t r i b u t i o n s o f the f i v e asymmetric c e n t r e s of methyl tallopyranoside  ( 6 3 ) , whose molecular r o t a t i o n ,  cx-D[M] , i s T  + 4 , 0 7 0 ° , a r e +a, -b, - c , -d and -e, and i n methyl £>-Dmannopyranoside ( 6 4 ) , ( [ M ] = M  - 1 3 , 3 9 0 ° ) , a r e -a, -b,  -c,  [ M ] + [ H ) = 2 ( - b - c - e ) , so that  +d and -e. T h e r e f o r e  T  M  [M]^ ,  the c a l c u l a t e d molecular r o t a t i o n o f the D-lyxo-lsomer, i s [M] + M /2 T  tion,  = - 4 , 6 6 0 ° , whence the c a l c u l a t e d  m  M/to,  s p e c i f i c rota-  i s -31°.  In a s i m i l a r manner the molecular r o t a t i o n (44) was obtained by h a l v i n g  the D-arabino-isomer  of the molecular r o t a t i o n s (65)  ( M  (66)  ( [MJJ = -18,430°).  of methyl  = 24,420°) and of methyl  A  (+a)  (+c)  HO-C-H H-C-OH  (-b)  (-e)  H - C ^ ^ ChyDH (44)  the sum  (3 -D-idopyranoside  T h i s gave a value of + 2 0 ° f o r •  H  V/  0 C H  3  HO^-H  (+c)  H-C-OH  ( d)  H-C-OH  (-e)  H-Q-  +  of  o^-D-altropyranoside  the s p e c i f i c r o t a t i o n of the D.-arabino-isomer  (-b)  [M]  /H  H3CO (-a) (-b)  6  (44) .  (+c) (-d)  T HO-C-H H-C-OH 6 HO-C-H  C-e)  HOH  2  (65)  HOH  "•2..  (66)  - 62 C a l c u l a t e d values  -  f o r the D - r l b o - ( 6 l ) and  B-xylo-(62)  Isomers, from the known molecular r o t a t i o n s of v a r i o u s methyl hexopyranosides and tabulated  below.  Observed  [p3  X  D  1,, 5-anhydro-  D - r i b o ( 6 l ) D-lyxo(6o) D-xylo(62) D-arabino(44)  Y o  ,-50°  1 , 5 - a n h y d r o h e x i t o l s , were as  C a l c u l a t e d [c*I of isomeric 4-deoxy-D-hexitols  D  other  ~ ' 46°  19  106°  "-31°  -34°  20°  67°  Comparisons of the observed r o t a t i o n s of p o l y o l s X and w i t h those c a l c u l a t e d f o r the f o u r p o s s i b l e then l e d to the c o n c l u s i o n  that p o l y o l X was (60),  anhydro-4-deoxy-D-lyxo-hexitol the D-arabino-isomer (44) .  and  stereoisomers 1,5-  probably  t h a t Y was  This conclusion  Y  probably  therefore  dis-  agreed w i t h the assignment of the D-arabino- c o n f i g u r a t i o n to F r a c t i o n I , which had  a s p e c i f i c r o t a t i o n of  Furthermore, Gorin's p o l y o l Y was t r i s - p - n l t r o b e n z o a t e , m.p.  c h a r a c t e r i s e d as  115-119°,  F r a c t i o n I gave a p - n i t r o b e n z o y l and  M  D  59°,  the  whereas  d e r i v a t i v e w i t h m.p.  215°  -50°.  I t was  then necessary to c o n s i d e r  that c o n f i g u r a t i o n a l lnversiomeihad of the oxo  -13°.  the  occurred  possibility during  r e a c t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l .  the  course  Certain  c i r c u m s t a n c i a l evidence can be mentioned which i n d i c a t e d t h a t the D - t h r e o - c o n f i g u r a t i o n r e t a i n e d during  this reaction.  of the six-membered r i n g Thus when  was  3,4-di-O-acetyl-  D - x y l a l was  r e a c t e d w i t h o n l y 2 moles of s y n t h e s i s gas, a  q u a n t i t y of unchanged g l y c a l was of the  isolated.  The  trans-arrangement  cx - g l y c o l system i n F r a c t i o n s I and I I was  by the f a c t that n e i t h e r compound formed  indicated  a d e r i v a t i v e with  acetone, as i t i s known that a c i s c o n f i g u r a t i o n i s a p r e r e q u i s i t e of i s o p r o p y l i d e n e a c e t a l f o r m a t i o n . Some e x p l o r a t o r y experiments were c a r r i e d out w i t h a view to s y n t h e s i s i n g the D-arabino-(44)  and  L-xylo-(45)  isomers of l,5-anhydro-4-deoxy-hexitol by an a l t e r n a t i v e r o u t e from 3 , 4 - d i - O - a c e t y l - D - x y l a l , whereby the p o s s i b i l i t y of r i n g i n v e r s i o n s was  absent.  The r e c e n t l y r e p o r t e d p r e 98 ^  p a r a t i o n by Goxon and F l e t c h e r  of. a 2,6-anhydro-heptItol  by r e d u c t i o n , f o l l o w e d by deamination of  2,3,4,6-tetra-0-  acetyl-£ -D-glucopyranosyl cyanide suggested the of employing  possibility  a s i m i l a r sequence b f r e a c t i o n s subsequent  td  the i n t r o d u c t i o n of a cyano- group a t C - l of the g l y c a l . It i s claimed^  0,  that hydrogen  cyanide r e a c t s w i t h  d e r i v a t i v e s of 2,3-dihydro-4H-pyran  ( l ) , i n the  of a b a s i c c a t a l y s t , w i t h f o r m a t i o n of tetrahydropyrans.  2-alkoxy  presence  6-cyano-2-alkoxy-  However no r e a c t i o n was  observed over  s e v e r a l hours when 3 , 4 - d i - O - a c e t y l - D - x y l a l (22) was i n anhydrous hydrogen  dissolved  c y a n i d e ^ i n the presence of sodium 1  c y a n i d e ; a p p a r e n t l y the double bond of g l y c a l s i s i n s u f f i 101 c i e n t l y a c t i v a t e d f o r t h i s a d d i t i o n to take p l a c e was  .  It  noted that 2-cyano-tetrahydropyran has been prepared  - 64  -  by the a d d i t i o n of hydrogen c h l o r i d e to the double bond of 2,3-dihydro-4H-pyran  ( l ) , f o l l o w e d by replacement  of c h l o r i d e  .102 by cyanide on r e f l u x i n g with s i l v e r cyanide i n e t h e r  J  l i t h i u m aluminum hydride r e d u c t i o n of the cyano- d e r i v a t i v e gave 2-aminomethyl-tetrahydropyran.  A similar preparation  of the cyano- d e r i v a t i v e from 2-bromo-tetrahydropyran has been e f f e c t e d by the a c t i o n of s i l v e r or mercuric When 3 , 4 - d i - O - a c e t y l - D - x y l a l (22) s o l u t i o n was product was  i n c o l d benzene syrupy  obtained on removal of s o l v e n t which e x h i b i t e d  a d d i t i o n of HC1  cm , -1  t h i s i n d i c a t i n g that q u a n t i t a t i v e  had o c c u r r e d across the double bond of the  R e a c t i o n of the product with mercuric'cyanide  nitromethane ^  not be p u r i f i e d by chromatography. present i n the 2000-2300 cm"  spectrum  in  gave a dark c o l o u r e d product which c o u l d  0  was  1 0  s a t u r a t e d w i t h dry hydrogen c h l o r i d e a  no a b s o r p t i o n at 1640  glycal.  cyanide ^.  1  Although  r e g i o n of the  , a n a l y s i s showed the presence  i n the chromatographed product.  no a b s o r p t i o n infrared  of 2.7$  nitrogen  R e f l u x i n g the H C 1 - a d d i t i o n  102 product w i t h s i l v e r cyanide i n e t h e r  apparently r e s u l t e d  i n no r e a c t i o n other than p a r t i a l r e g e n e r a t i o n of  (22).  Though these experiments were u n s u c c e s s f u l , they  de-  monstrated the f a c t that hydrogen c h l o r i d e adds r e a d i l y across the double bond of 3 , 4 - d i - O - a c e t y l - D - x y l a l ( 2 2 ) , formation of 3 , 4 - d i - 0 - a c e t y l - 2 - d e o x y - D - x y l o p y r a n o s y l (67).  Davoll  1 0  ^ has r e p o r t e d the s i m i l a r a d d i t i o n of  with  chloride HC1  (22)  HC1  >  o  H,CI  46  AcO (67)  (and HBr) t o I f , 4 - d i - 0 - a c e t y l - D ~ a r a b i n a l was  not s t a b l e , and was  ( 3 2 ) ; the  not c h a r a c t e r i s e d .  product  I t was  observed  t h a t the a d d i t i o n product of hydrogen c h l o r i d e t o (22)  also  tended to decompose on s t a n d i n g at room temperature ( i n c h l o r o f o r m s o l u t i o n ) , and a b s o r p t i o n i n the i n f r a r e d spectrum.  a t 1640  In t h i s r e s p e c t  resemble 2 , 3 - d i h y d r o - 4 H ~ p y r a n  cm"^  reappeared  the g l y c a l s  ( l ) which q u a n t i t a t i v e l y adds  hydrogen c h l o r i d e and hydrogen bromide, but the r e a d i l y dehydrohalogenated products have not been i s o l a t e d , and a r e  106,107 normally r e a c t e d  in situ  .  An a l t e r n a t i v e approach  to the problem i n hand was based on t h i s observed  addition:  a methyl, r a t h e r than a hydroxymethyl group, was  introduced  at C - l of the s i x -member ed r i n g of (22),  3,4-di-0-acetyl-I)-xylal  and the products thereby o b t a i n e d were i d e n t i f i e d  w i t h those r e s u l t i n g from r e d u c t i o n  of the t e r m i n a l  hydroxy-  methyl groups of the two l , 5 - a n h y d r o - 4 - d e o x y - h e x i t o . l s , Fractions  I and I I .  The a c t i o n of a l i p h a t i c or aromatic G r i g n a r d reagents on s p e c i f i c f u n c t i o n a l groups of carbohydrates has been developed by Bonner and co-workers  as a v e r s a t i l e t o o l  - 66 f o r the i n t r o d u c t i o n o f a l k y l or a r y l groups i n t o p o s i t i o n s o f the molecule. are  observed;  1.  Normal Grignard  such as l a c t o n e s , 2.  Metathetical  In general,  various  two types of r e a c t i o n  a d d i t i o n i n v o l v i n g carbonyl  functions,  e s t e r s and aldehydes, reactions.  Of the second type, r e a c t i o n s o f p a r t i c u l a r i n t e r e s t are those o f Grignard halides.  reagents w i t h p o l y a c e t y l - g l y c o s y l  S t r u c t u r a l l y these compounds are herniacetal h a l i d e s  and therefore resemble  oc - c h l o r o - e t h e r s ,  been known t o r e a c t w i t h Grignard  which have  long  reagents i n the f o l l o w i n g  109 manner  CI  R<  R-CH  +  R'MgX  >  R-CH  OR  +  MgXCl  OR  Although the r e a c t i o n s o f p o l y a c e t y l - g l u c o s y l h a l i d e s Grignard 1906  1 1 0  reagents has been a s u b j e c t '  1 1 1  47_  '  1 1 2  ,  with  of i n t e r e s t since  i t was not u n t i l 19^5 that Hurd and B o n n e r  1 1 3  demonstrated metathesis i n v o l v i n g the h e m i a c e t a l h a l i d e , according  t o equation 47_.  The observations  of a d d i t i o n product f o r m a t i o n  111  o f p r e v i o u s workers  , o r r e a c t i o n only o f the  110 a c e t y l groups w i t h Grignard  reagent  was accounted f o r by  the f a c t that an i n s u f f i c i e n t amount o f the reagent was used, or that the r e a c t i o n had been attempted at too low a temperature,  - 6? Bonner  114  showed that p r e f e r e n t i a l a d d i t i o n of G r i g n a r d r e -  agent occurs a t the e s t e r groups b e f o r e the m e t a t h e t i c a l r e a c t i o n takes p l a c e t o any a p p r e c i a b l e extent; as each e s t e r f u n c t i o n takes up 2 moles o f Grignard reagent 48),  (equation  complete r e a c t i o n o f a t e t r a - O - a c e t y l - g l y c o s y l h a l i d e  (equation 49) t h e r e f o r e r e q u i r e s the presence o f nine moles  RMgX^  of the reagent.  Thus when 2 , 3 , 4 , 6 - t e t r a - O - a c e t y l - c x -D-  glucopyranosyl chloride  (68) was r e f l u x e d i n ether w i t h  12 moles of phenyl magnesium bromide, c r y s t a l l i n e tetra-O-acetyl-(3-D-glucopyranosyl)-benzene panied by the syrupy  (2,3/4,6-  ( 6 9 ) , accom-  oc-anomer, was i s o l a t e d a f t e r r e a c e t y l a .  113  tion"  CHQAc OAc  (68)  C H OAc _+ 9C H MgBr  ;  CI OAc  6  5  —>  OAc  /  AcO OAc  (69)  i-f ex -anomer  ^  R e t e n t i o n o f c o n f i g u r a t i o n d u r i n g the f o r m a t i o n and subsequent decomposition o f the G r i g n a r d adduct t o the e s t e r f u n c t i o n (equation 48) formed the b a s i s of Bonner's  investi-  g a t i o n o f t h i s r e a c t i o n , which was undertaken t o determine whether the f o r m a t i o n o f the same type of product by the aluminium c h l o r i d e c a t a l y s e d g l y c o s y l a t i o n of aromatic 115 compounds  was accompanied  tions or inversions.  by i n t r a m o l e c u l a r i s o m e r i s a -  That c o n f i g u r a t i o n i s r e t a i n e d on de-  a c e t y l a t i o n by G r i g n a r d reagents i s a l s o a fundamental r e quirement o f our experiment.  T h i s p o i n t i s proved e x p e r i -  m e n t a l l y by the f a c t that D-glucose i s o b t a i n e d when 1 , 2 , 3 , 4 , 6 p e n t a - 0 - a c e t y l - 6 -D-glucose i s r e a c t e d w i t h G r i g n a r d r e agents  112  .  ~  '  The m e t a t h e t i c a l r e a c t i o n of G r i g n a r d reagents w i t h the a c e t y l a t e d h a l l d e s o f D-glucose, D-xylose and l a c t o s e was found by Hurd and Bonner  t o be an e x c e l l e n t g e n e r a l  procedure f o r the p r e p a r a t i o n o f a l d o p y r a n o s y l d e r i v a t i v e s of aromatic (benzene, t o l u e n e , naphthalene) and a l i p h a t i c (butane, isopropane) hydrocarbons. Yoshimura  By the same procedure,  and co-workers have prepared the analogous phenyl,  b e n z y l , methyl, e t h y l , p r o p y l and b u t y l d e r i v a t i v e s of 2 -  116 amino-2-deoxy-D-glucose  .  The r e a c t i o n , d e s c r i b e d below,  of a G r i g n a r d reagent w i t h a 2-deoxy-glyeosyl h a l i d e , d e r i v e d from a g l y c a l , i s a h i t h e r t o unexplored aspect o f t h i s g e n e r a l synthesis.  69 Hydrogen c h l o r i d e was of 3,4-di-O-acetyl-D-xylal  added a c r o s s the double bond  (22)  s o l u t i o n of the syrupy product  (equation 46), and an e t h e r e a l (67)  was  added to a p r e v i o u s l y  prepared s o l u t i o n of methyl magnesium bromide c o n t a i n i n g a t w o - f o l d excess of the G r i g n a r d reagent moles). was  R e a c t i o n and decomposition  (approximately  of the r e a c t i o n  c a r r i e d out a c c o r d i n g to the procedure  108  Bonner  , except t h a t the product was  i n the d e a c e t y l a t e d form, as i t was s e p a r a t i o n by paper chromatography. of the syrup which was  10  mixture  d e s c r i b e d by  i s o l a t e d at t h i s  stage  hoped t o e f f e c t a However, chroma togiaris  i s o l a t e d , on d e v e l o p i n g w i t h a variety  of d i f f e r e n t sovent systems,  r e v e a l e d only one compact zone •73  on s p r a y i n g w i t h sodium p e r i o d a t e - S c h i f f reagent  .  S e p a r a t i o n of t h i s component from any I m p u r i t i e s not r e v e a l e d by the spray reagent was  e f f e c t e d by p r e p a r a t i v e paper  chromatography, and the p u r i f i e d m a t e r i a l was to n.m.r. a n a l y s i s .  The  spectrum  then s u b j e c t e d  o b t a i n e d i n deuterium i  oxide s o l u t i o n c l e a r l y showed t h a t the a p p a r e n t l y homogeneous product was  a mixture of two compounds, both c o n t a i n i n g a  C-CHg grouping, reaction  A  OAc \C  AcOM (67)  (and t h e r e f o r e i n d i c a t e d t h a t the  (equation 50)  >HCI  5CH^MgBr 1  had  ^  attempted  succeeded).  50  - 70 T h i s was  apparent from the presence of a p a i r of o v e r l a p p i n g  doublets  ( J = 6 c/s) at h i g h f i e l d ,  In  8 = 1.14  and 1.17  a d d i t i o n to t h i s a b s o r p t i o n i n the C-methyl r e g i o n of spectrum, a m u l t i p l e t around 8 = 1.8 ppm was  the  assignable  m u l t i p l e t between 3 . 0 and 4 . 2  to  C-GH^-C, and a complex c  to  the remaining hydrogens of the r i n g s J the e n t i r e  was of  ppm.  spectrum  thus i n d i c a t i v e of a mixture of the two anomeric (2-deoxy-D-xylbpyranosyl)-methane.  ppm  forms  R e t a i n i n g the p r e v i o u s  nomenclature, these were l , 5 - a n h y d r o - 4 , 6 - d i d e o x y - D - a r a b i n o hexitol  (70'), and 1,5-anhydro-4,6-dideoxy-L-xylo-hexitol (7l) •  The r e l a t i v e I n t e n s i t i e s of the two methyl d o u b l e t s showed t h a t the two components were present i n a r a t i o of about  3 2. :  R e s o l u t i o n of t h i s mixture presented a problem which was  s o l v e d by g a s - l i q u i d p a r t i t i o n chromatography  the  acetylated anhydrodldeoxyhexitols.  (GLPC) of  A c e t y l a t i o n of a  p o r t i o n of the mixture w i t h a c e t i c a n h y d r i d e - p y r i d i n e a syrupy product which on t h i n l a y e r chromatography the  gave  showed  presence of two b a r e l y - r e s o l v e d components! t h i s  was  f u r t h e r v e r i f i c a t i o n t h a t the I n i t i a l product i s o l a t e d from the  G r i g n a r d r e a c t i o n was a mixture d e s p i t e i t s apparent  homogenlety  on paper chromatography.  After preliminary  periments to e s t a b l i s h s u i t a b l e c o n d i t i o n s , i t was to  ex-  possible  r e s o l v e the mixture of a n h y d r o d i d e o x y h e x i t o l a c e t a t e s  i n t o two d i s t i n c t  zones by GLPG, u s i n g a column  (10' x  W')  - 71  -  of 20$ S i l c o n e GE-SF-96 on f i r e b r i c k at 1 8 0 ° ,  I f the amount  of mixture a p p l i e d to the column In s o l u t i o n was small.  R e s o l u t i o n was  s e p a r a t i o n was and i t was  l e s s s a t i s f a c t o r y when a p r e p a r a t i v e  attempted  (approximately 5 tng per  injection),  necessary to c o l l e c t f r a c t i o n s e n r i c h e d i n each  component and rechromatograph  these i n order to o b t a i n each  component i n a pure s t a t e , uncontaminated Isomer.  sufficiently  by the other  Each pure component gave an elemental a n a l y s i s i n  agreement w i t h an e m p i r i c a l formula of C H g O ^ . 10  1  The  moving the two components ( r e l a t i v e r e t e n t i o n time -21°,  was  1.00),  more d e x t r o r o t a t o r y than the slower component  ( r e l a t i v e r e t e n t i o n time 1 . 1 0 ) , which had a s p e c i f i c of - 8 2 ° .  rotation  Groups of s i g n a l s present In the n.m.r. spectrum  of each f r a c t i o n , measured In carbon t e t r a c h l o r i d e were r e a d i l y a s s i g n e d from t h e i r resonance relative intensities (2),  faster-  acetyl  (6)  ( i n parentheses)  solution,  positions  to C-CH3 ( 3 ) ,  and C-CHg-C (5),  and r i n g hydrogens w i t h an Oc-oxygen  and confirmed the i d e n t i t i e s of the two  components as  iso-  meric 2 , 3 - d i - 0 - a c e t y l - 1 , 5 - a n h y d r o - 4 , 6 - d i d e o x y - h e x i t o l s . On the b a s i s t h a t no i n v e r s i o n of c o n f i g u r a t i o n was as a r e s u l t of the r e a c t i o n of (67)  possible  w i t h the G r i g n a r d r e -  agent, one of the separated Isomers had the D-arabinoand the other the L - x y l o - (73)  configuration.  (72),  - 72 -  (70) +• (71)  Ac 0/pyridine o  >  51  These same two a n h y d r o d i d e o x y h e x i t o l d i a c e t a t e s were then s y n t h e s i s e d by an a l t e r n a t i v e route from the mixture of two i s o m e r i c  2,3-di-0-acetyl-l,5-anhydro-4-deoxy-hexitols  (74) and (75)* which formed the major p a r t o f the r e a c t i o n product from the hydroxymethylation xylal  of  3,4-di-O-acetyl-D-  ( 2 2 ) , and from which F r a c t i o n s I and I I were obtained  on d e a c e t y l a t i o n . T h i s s y n t h e s i s i n v o l v e d only the f r e e primary h y d r o x y l groups a t C - 6 , which were reduced  to methyl :  groups by a s e r i e s o f r e a c t i o n s which have been a p p l i e d p r e v i o u s l y t o the p r e p a r a t i o n of 6-deoxy-sugars, such as 6-deoxy-D-glucose  117  and 6-deoxy-D-galactose ®, from the 11  parent a l d o s e s .  QHpTs  CH 0H 2  (22)  CO/Hg^  —Q CKOH  AcQ  OAc  (75)  - 73 -  Ra N i  Nal  ^  ((70) + ( 7 D )  OH 1.  (78)  GLPC  2.  (79) V  (72) + (73)  A p o r t i o n o f the syrupy mixture r e s u l t i n g from the oxo r e a c t i o n o f 3 , 4 - d i - O - a c e t y l - D - x y l a l (22) was t r e a t e d w i t h an excess of p - t o l e u n e s u l p h o n y l c h l o r i d e i n p y r i d i n e under standard c o n d i t i o n s , and on working  up the r e a c t i o n  mixture a product was o b t a i n e d which, from an examination of the i n t e n s i t i e s of the c h a r a c t e r i s t i c resonances n.m.r. spectrum  i n the  a s s o c i a t e d w i t h the p - t o l y l s u l p h o n y l group,  r e l a t i v e t o those due t o a b s o r p t i o n by the a c e t y l  groups,  c o n t a i n e d approximately 75$ o f the i s o m e r i c 6-0-ptolysulphonyl derivatives i n acetone  (76) and (77)•  The crude  product,  s o l u t i o n , was then heated i n a s e a l e d tube i n  the presence  o f sodium i o d i d e , whereby the t o s y l o x y groups 1  were r e p l a c e d by i o d i d e t o g i v e the corresponding  mixture  of 6 - d e o x y - 6 - i o d o - d e r i v a t i v e s (78) and ( 7 9 ) , and sodium p-toluenesulphonate was. p r e c i p i t a t e d .  On c o o l i n g and f i l 9  t r a t l o n , the amount, of sodium p-toluenesulphonate'''<Lsolated agreed c l o s e l y with the o r i g i n a l e s t i m a t i o n , from n.m.r.  - 74 data, of the content o f i s o m e r i c 6 - 0 - p - t o l y l s u l p h o n y l derivatives  (76)  and (77)  of the r e a c t i o n products  i n the crude mixture. (78)  and (79)  Isolation  from r e s i d u a l sodium  i o d i d e was achieved by e v a p o r a t i o n of the f i l t r a t e t o dryness and e x t r a c t i o n w i t h e t h e r .  When the r e s u l t i n g  i n s l i g h t l y b a s i c methanol s o l u t i o n , wa3 hydrogenated atmospheric  pressure and temperature  product, at  i n the presence of  Raney n i c k e l , a c c o r d i n g to the procedure  of Freudenberg  118 and Raschig  , hydrogen was r a p i d l y absorbed  t u r e was s i m u l t a n e o u s l y d e a c e t y l a t e d .  and the mix-  From t h i s  reaction  a syrup was i s o l a t e d which showed o n l y one zone by paper chromatography, i d e n t i c a l i n Rp value to t h a t of the product o b t a i n e d from the r e a c t i o n of xylopyranosyl chloride  3,4-di-0-acetyl-2-deoxy-D-  (67) w i t h methyl magnesium bromide,  and which, a f t e r p u r i f i c a t i o n by paper chromatography, had a n.m.r. spectrum which was e s s e n t i a l l y I d e n t i c a l to t h a t previously obtained. two D-arablno-  (70)  That t h i s was a mixture of the same and L - x y l o - (71)  4 , 6 - d i d e o x y h e x I t o l was demonstrated  forms of 1,5-anhydroby a c e t y l a t i o n of the  p u r i f i e d product and f r a c t i o n a t i o n by GLPC into two  compon-  ents. D -23°  a  n  d  - 8 1 ° , which had n.m.r. spectra  i d e n t i c a l w i t h those of the two Isomeric 2 , 3 - d i - 0 - a c e t y l - l , 5 a n h y d r o - 4 , 6 - d i d e o x y - h e x i t o l s (72) and ( 7 3 ) , p r e v i o u s l y de1 •  • •  scribed.  - 75 Thus, the f a c t that the same two compounds were obt a i n e d by e i t h e r route  (equations  50 and 52)  e s t a b l i s h e d t h a t the secondary hydroxyl  conclusively  groups o f F r a c t i o n s  I and I I had r e t a i n e d the D-threo- c o n f i g u r a t i o n in 3j4-di-0-acetyl-D-xylal.  present  I t was then p o s s i b l e t o s t a t e  w i t h c e r t a i n t y that F r a c t i o n I was l,5-anhydro-4-deoxy-I)arabino-hexltol  ( 4 4 ) , and t h a t F r a c t i o n I I was 1 , 5 - a n h y d r o - 4 -  deoxy-L-xylo-hexitol  (45).  Though not an e s s e n t i a l part of t h i s p r o o f ,  i t was  of i n t e r e s t t o i d e n t i f y i n d i v i d u a l l y the two isomeric d i acetates  (72) and (73) which were separated by GLPC. . I t  i s known that primary hydroxyl sulphonyl  groups r e a c t w i t h p - t o l u e n e -  c h l o r i d e a t a much f a s t e r r a t e than do secondary  119 hydroxyl  groups  sulphonylate  ; i t i s therefore possible to p r e f e r e n t i a l l y  a r e a c t i v e primary p o s i t i o n even when other  vacant h y d r o x y l s are present.  The procedure o f unimolar  s u l p h o n y l a t i o n , . e m p l o y i n g an amount o f the s u l p h o n y l  chloride  i n s l i g h t excess o f that r e q u i r e d f o r e s t e r i f i c a t l o n o f the one  r e a c t i v e s i t e , was f i r s t  introduced  by Ohle and Dickhauser  93 and  l a t e r improved by Levene and Raymond  .  G e n e r a l l y the  r e a c t i o n r a t e i s lowered by c o o l i n g , thereby f u r t h e r the p o s s i b i l i t y of a c y l a t i o n o f the secondary 1,5-Anhydro-4-deoxy-L-xylo-hexito1 ( 4 5 ) , from the  chromatographic s e p a r a t i o n  reducing  hydroxyls. (Fraction II  o f the d e a c e t y l a t e d  - 76 " hydroxymethylation product from 3 , 4 - d i - O - a c e t y l - D - x y l a l ) was s u b j e c t e d to unlmolar t o s y l a t i o n  ( l . l molar e q u i v a l e n t s of 18  p-toluenesulphonyl c h l o r i d e ) , with cooling i n ice J a f t e r hours a c e t i c anhydride was  then added i n order t o a c e t y l a t e  the secondary h y d r o x y l groups and f a c i l i t a t e i s o l a t i o n of the product.  The r e s u l t i n g syrup, which showed a b s o r p t i o n  i n the i n f r a r e d spectrum ( C h a r a c t e r i s t i c of both a c e t y l p - t o l y l s u l p h o n y l groups  (S=0  s t r e t c h i n g and aromatic  s t r e t c h i n g v i b r a t i o n s ) , but not of h y d r o x y l , was  and C=C  not f u r t h e r  I t c o n t a i n e d approximately 80$ of 2 , 3 - d i - O - a e e t y l -  purified.  l,5-anhydro-4-deoxy-6-0-(p-tolylsulphonyl)-L-xylo-hexitol as judged by the amount of sodium p-toluenesulphonate was  formed when the crude d e r i v a t i v e was  (77)>  which  subsequently heated  i n a s e a l e d tube w i t h sodium i o d i d e i n acetone, d u r i n g the c o n v e r s i o n of (77)  to the 6 - d e o x y - 6 - i o d o - d e r i v a t i v e  Reductive dehalogenation of (79)  (79)•  In the presence of Raney  121 nickel  1,5-  , and simultaneous d e a c e t y l a t i o n , then gave  anhydro-4,6-dideoxy-L-xylo~hexito.l ( 7 3 ) . l a t i o n , t h i s was  Following reacety-  r e a d i l y i d e n t i f i e d by GLPC with'the  faster-  moving of the two components present i n the mixture of d i d e o x y h e x i t o l d i a c e t a t e s obtained by the two routes described previously. of the two  ( M  D  -21°)  was  dideoxy-L-xylo-hexitol (73), was  anhydro-  alternative  Thus the more d e x t r o r o t a t o r y 2,3-di-0-acetyl-1,5-anhydro-4,6and the isomer having . [ p 3  the corresponding D-arabino- isomer  (72).  D  -82°  _ 77  (v)  j-  I d e n t i t i e s of P o l y o l s X and Y Prom the r e s u l t s d i s c u s s e d  8 2  i n the previous pages, i t 82  was c l e a r that Gorin's assignment f i g u r a t i o n to the dextrorotatory (referred to previously  of the D-arabino- conl,5-anhydro-4-deoxyhexitol,  as P o l y o l Y ) , I s o l a t e d from the  products of h y d r o g e n o l y s i s of methyl (51)  80  » was i n c o r r e c t .  oc-D-glucopyranoside  —  Prom a c o n s i d e r a t i o n  of the a v a i l a b l e  evidence, i t was p o s s i b l e t o deduce the i d e n t i t y of t h i s compound.  I t was known t o be of the D - s e r i e s ,  and Gorin's  study of the r e l a t i v e r a t e s of l e a d t e t r a a c e t a t e i n d i c a t e d a t r a n s arrangement of the  consumption  o<-glycol group of Y.  Consequently, i t was c o n s i d e r e d that p o l y o l Y was, i n f a c t , the a l t e r n a t i v e trans_-isomer, 1,5-anhydro-4-deoxy-D-xyloh e x i t o l ( 6 2 ) , and t h e r e f o r e the L-xylo-isomer ( 4 5 ) . ..  the enantiomer of F r a c t i o n I I ,  """"  Through the k i n d c o o p e r a t i o n of Dr. G o r i n i n supplying a sample o f the t r i s - p - n l t r o b e n z o y l d e r i v a t i v e of h i s p o l y o l , i t was p o s s i b l e  to prove t h i s p o i n t .  Debenzoylation of the  d e r i v a t i v e w i t h r e f l u x i n g methanollc sodium methoxide gave the of and  syrupy p o l y o l , which was found t o havj a s p e c i f i c r o t a t i o n +40°,  equal and o p p o s i t e t o that of the L-isomer  (45),  which had a n.m.r. spectrum i n deuterium oxide s o l u t i o n  i d e n t i c a l w i t h that of (45) .  The syrupy compound formed a*  c r y s t a l l i n e t r i - O - a c e t y l d e r i v a t i v e , m.p. 8 0 - 8 2 ° ,  & d j ) +40°,  whose i n f r a r e d spectrum was i d e n t i c a l w i t h that of 2 , 3 , 6 - t r i -  - 78 0 -a c e ty 1 -1,5 -a nhydr o -4 -deoxy -L-xylo -hex It or, [pc]  D  m.p.  80-81°,  _4i°. Comparison o f a sample of the c r y s t a l l i n e ,  t o r y anhydrodeoxyhexitol  levorccta-  ( P o l y o l X ) , a l s o isolated®  from  2  the h y d r o g e n o l y s i s r e a c t i o n o f (51), w i t h 1,5-anhydro-4deoxy-D-lyxo-hexitol  ( 6 0 ) , one o f the products  obtained  —  from the oxo r e a c t i o n o f 3 , 4 - d i - O - a c e t y l - D - a r a b i n a l (32)  122  ,  confirmed Gorin's assignment of the s t r u c t u r e o f t h i s compound.  I t i s noteworthy t h a t the true s p e c i f i c r o t a t i o n o f  each p o l y o l  (X and Y) was some 20-30° lower than the values  c a l c u l a t e d from an a p p l i c a t i o n o f the r u l e s of o p t i c a l superposition (vl)  (page  Proton Magnetic  62) . „ Resonance and S t e r e o c h e m i s t r y o f  F r a c t i o n s I and I I I t was p r e v i o u s l y noted  (page  4 4 ) t h a t the resonance  p o s i t i o n s and i n t e n s i t i e s o f the h i g h f i e l d  signals  attri-  buted t o the C-4 hydrogens of (44) and (45), p r o v i d e d  evi-  dence f o r t h e i r s t r a i g h t c h a i n anhydrodeoxyhexitol s t r u c t u r e , r a t h e r than the branched  c h a i n s t r u c t u r e s (46) and (47).  the case of one of the isomers, hexitol  In  1,5-anhydro-4-deoxy-L-xylo-  (45), a d d i t i o n a l s t e r e o c h e m i c a l i n f o r m a t i o n c o u l d  be gained from an i n s p e c t i o n of the m u l t i p l i c i t i e s o f the s i g n a l s i n t h i s r e g i o n , as w e l l as from the resonance  posi-  t i o n s of the i n d i v i d u a l C-4 protons, which was, i n complete  - 79. ~ agreement w i t h the s t r u c t u r e a s s i g n e d on the b a s i s o f the chemical evidence d e s c r i b e d i n the preceeding pages. Present knowledge o f the r e l a t i o n between c o n f i g u r a t i o n s and conformations magnetic  resonance  of carbohydrates and t h e i r n u c l e a r  stems from the p i o n e e r i n g work o f Lemieux, 123  K u l l n i g , B e r n s t e i n and Schneider  .  Two f a c t o r s o f impor-  tance a r e the angular dependence o f s p i n - s p i n c o u p l i n g constants,, and the dependence of chemical s h i f t s on molecular geometry. pyranose  During t h e i r i n v e s t i g a t i o n s o f v a r i o u s a c e t y l a t e d sugars, Lemieux and co-workers observed that the  s p l i t t i n g o f the anomeric protton H^, which i s r e a d i l y d i s c e r n a b l e being at lowest f i e l d , was dependent on the r e l a t i v e o r i e n t a t i o n o f Hg, w i t h which i t was coupled. J  When  and Hg were t r a n s - d i a x i a l , the s p i n - s p i n c o u p l i n g constant ,=,TT was two--to three' ti'mes l a r g e r than when the neighbouring l' 2 v  n  w  a  hydrogens were i n other • o r i e n t a t i o n s equatorial-equatorial).  (axial-equatorial or  Thus a l a r g e c o u p l i n g constant was  a s s o c i a t e d w i t h a d i h e d r a l angle  ( 0 ) o f 1 8 0 ° , and a s m a l l e r  c o u p l i n g constant w i t h a d i h e d r a l angle o f 6 0 ° .  T h i s ex-  p e r i m e n t a l l y observed angular dependence of c o u p l i n g constants was l a t e r g e n e r a l i s e d by K a r p l u s  124 36 '  .  I n the course o f the same i n v e s t i g a t i o n on a c e t y l a t e d 123 pyranose  sugars, Lemieux and co-workers  f e r e n c e i n resonance  observed a d i f -  positions f o r chemically i d e n t i c a l  gens which was r e l a t e d t o t h e i r o r i e n t a t i o n s i n space.  hydroThus  i n l , 2 , 3 , 4 - t e t r a - 0 - a c e t y l - (5 -D-xylose ( 8 0 ) , the e q u a t o r i a l hydrogen a t C-5 was at lower f i e l d than the C-5 a x i a l hydrogen; s i m i l a r l y , e q u a t o r i a l anomeric hydrogens i n v a r i a b l y resonated a t lower magnetic f i e l d than t h e i r a x i a l c o u n t e r parts.  The p o r t i o n o f the spectrum o f (80) due t o the methy-  H(X) \ MM) AcO  v v  "  (80)  lene hydrogens a t the C-5 p o s i t i o n was of p a r t i c u l a r I n t e r e s t , as i t was p o s s i b l e t o d e r i v e parameters f o r the chemical s h i f t s and s p i n c o u p l i n g equatorial  c o n s t a n t s f o r the i n d i v i d u a l  (A) and a x i a l (B) hydrogens a t t a c h e d t o the same 125  carbon atom, when t r e a t e d as an ABX system t a i n e d were:  J  A  B  = 12 c/s;  J  B  X  = 8 c/s;  . J  = A  X  Values ob3.2 c/s.  126 More r e c e n t l y , Woo, Dion and Johnson  have made  use o f the r e l a t i o n s h i p s e s t a b l i s h e d by Lemieux and co-workers i n deducing the complete c o n f i g u r a t i o n s (8l)  and o f c h a l c o s e  b i o t i c chalcomycin.  of methyl  chalcoside  ( 8 2 ) , d e g r a d a t i o n products o f the a n t i T h e i r assignment o f the c o n f i g u r a t i o n s  123  - 81 -  at C-3 and C-5 o f ( 8 l ) , from the m u l t i p l i c i t i e s of the G-4 p r o t o n s i g n a l s , w i l l be d e s c r i b e d , as the s t e r e o c h e m i s t r y of the C-3 - C-4 - C-5 fragment of t h i s molecule c l o s e l y resembles t h e c o r r e s p o n d i n g p o r t i o n of l , 5 - a n h y d r o - 4 - d e o x y L - x y l o - h e x i t o l (45), and t h e r e f o r e p r o v i d e s a model on which to base a d i s c u s s i o n of the h i g h f i e l d p o r t i o n o f the spectrum of the l a t t e r compound.  With r e f e r e n c e t o F i g u r e 1A, which  shows the s i g n a l s o f the C-4 methylene group o f methyl c h a l c o s i d e measured around  8  i n p y r i d i n e s o l u t i o n ; the lower f i e l d  group  = 2.05 ppm was a s s i g n e d t o the e q u a t o r i a l hydrogen  ( H ^ ) , and the broad group o f s i g n a l s a t 8 e  -  1 . 0 0 t o 1.58  ppm, p a r t i a l l y obscured by the C-methyl doublet, t o the a x i a l hydrogen  ( H ^ ) . Each group of s i g n a l s was c o n s i d e r e d 125 • ' •• as an ABX system r e s u l t i n g from c o u p l i n g between H, , H *+e HQ g  and one o f the n e i g h b o u r i n g protons on C-3 o r C-5, the r e s u l t i n g l i n e s then being f u r t h e r s p l i t by a f o u r t h hydrogen (on C-5 or C - 3 ) .  On the b a s i s of the o b s e r v a t i o n s o f Lemieux  and co-workers  the s p i n - s p i n c o u p l i n g between the two C-4  - 82  -  hydrogens would be expected to be l a r g e , of the order of 12  c/s J a d d i t i o n a l c o u p l i n g of each proton w i t h  protons on C-3  and C-5  neighbouring  would a l s o be l a r g e i f a d i a x i a l r e -  l a t i o n s h i p e x i s t e d , otherwise served s p l i t t i n g of H^  e  i t would be s m a l l .  i n t o two  The  q u a r t e t s indeed showed the  a n t i c i p a t e d l a r g e c o u p l i n g (12.5  c/s) w i t h the geminal  but gave no a d d i t i o n a l i n f o r m a t i o n on the r e l a t i v e t i o n of H» and H  3  .  a  was  1^4 4 J  3  a  a  n  d  J  4a  4e^  w  i  t  s i g n a l , 34.5  g  h  w  h  i  coupled to the e q u a t o r i a l C-4  c/s, J ^  the  ^  a  +  J  4  a  c/s, t h i s being  c  h  t  h  e  a x i a l C-4  hydrogen  hydrogen and to the  and C - 5 .  Thus, as J ^  a  two^  g  was  5 must be 22 c/s; t h i s l a r g e v a l u e  c o u l d only be r a t i o n a l i s e d i f H^ and H^ were both  axial.  j - and J., „ satisfactorily 4 a , d° , _j3 f o r the observed s p l i t t i n g p a t t e r n of H ^ ; the two  Values of 11 accounted  orienta-  of t h r e e c o u p l i n g constants  neighbouring hydrogens on C-3 12.5  a  5  p r a c t i c a l l y equal to the sum J  H^ ,  However these c o u l d be deduced from  width of the h i g h e r f i e l d H^  ( 4  ob-  e/s f o r both J,  e q u a t o r i a l - a x i a l i n t e r a c t i o n s of H,  were a s s i g n e d J values  4e of  2.1  of  the lower f i e l d  and $.0 c/s to account  The C-4  to  p o r t i o n of the n.m.r/ spectrum  of 1,5-anhydro-  measured i n deuterium  oxide  ( F i g u r e 1 B) i s seen to bear a c l o s e resemblance  the corresponding p o r t i o n of the spectrum  coslde  multiplicity  group.  4-deoxy-L-xylo-hexltol (45), solution  f o r the observed  (8l)J  of methyl c h a l -  the main p o i n t of d i f f e r e n c e i s t h a t the  chemical  Nmr Spectra (C-4 protons) of : A ' M e t h y l c h a l c o s i d e  Figure I  : B  fraction  II  : C  Fraction I  -83  -  s h i f t between a x i a l and e q u a t o r i a l hydrogens at C-4 o f (45) i s l e s s than was the case w i t h H^  and H^^ of ( 8 l ) , con-  a  sequently t h e r e i s no s e p a r a t i o n between the lower and h i g h e r f i e l d groups o f s i g n a l s . e q u a t o r i a l hydrogen s i g n a l around  field  The s p l i t t i n g of the  8 = 2 . 0 ppm c l e a r l y shows  the l a r g e s p i n - s p i n c o u p l i n g t o the geminal hydrogen ( J 2 j , 4 e a  approximately 12.5  c / s ) , and f u r t h e r s m a l l s p l i t t i n g s by  c o u p l i n g t o the adjacent hydrogens on C-3 and C-5 t o g i v e a t o t a l of 8 l i n e s . hydrogen on C-4 H  c  The width of the s i g n a l o f the a x i a l  (about 35 c/s) l e a v e s no doubt t h a t  and  a r e both a x i a l , as the sum of t h e i r c o u p l i n g constants  w i t h H^  a  Is approximately 22 c / s , as was the case w i t h  methyl  chalcoside. The corresponding p o r t i o n of the spectrum anhydro-4-deoxy-D~arabino-hexito1  (44)  of  1,5-  ( F i g u r e 1 C) was not  amenable t o s i m i l a r a n a l y s i s ; a m u l t i p l e t was observed between  8 =1.38  and 2.15  ppm which c o u l d not be separated  i n t o a x i a l and e q u a t o r i a l  signals.  Deuterated Analogues o f (44) and (45) S e v e r a l methods are known f o r s i m p l i f y i n g , or otherwise m o d i f y i n g , proton magnetic resonance f a c i l i t a t e t h e i r assignments,  s p e c t r a i n order to  and a number of these  experi-  127 mental techniques have been d i s c u s s e d by H a l l  .  As an  example o f a simple a i d t o s p e c t r a l refinement may be  - 84  -  mentioned the measurement of the s p e c t r a of p o l y o l s i n deuterium oxide, whereby h y d r o x y l l c hydrogens by deuterium.  are  exchanged  A more v e r s a t i l e , though l e s s r e a d i l y  avail-  a b l e technique i s the replacement of carbohydrate r i n g hydrogen atoms by deuterium.  Although deuterium has a n u c l e a r  s p i n i t s c o u p l i n g w i t h adjacent r i n g hydrogens  i s so s m a l l  t h a t t h e i r s i g n a l s are merely broadened and show no a b l e c o u p l i n g w i t h the deuterium.  resolv-  Consequently, although  proton resonance s p e c t r a are on the one hand by the s u b s t i t u t i o n of deuterium f o r hydrogen  simplified i n the mole-  c u l e , t h e r e i s at the same time a l o s s of r e s o l u t i o n i n thes i g n a l s of remaining hydrogens which are a d j a c e n t to the. deuterium atoms.  T h i s disadvantage can be overcome by the 127 technique of double resonance, or s p i n d e c o u p l i n g . Very few examples of the use of d e u t e r a t e d analogues as an a i d t o the assignment 128 129 reported  '  y i  of carbohydrate s p e c t r a have as y e t been  130 , and double resonance experiments have  J  been c o n f i n e d t o the removal of s p i n c o u p l i n g between i n t e r acting p r o t o n s ^ * ^ . 1  1  The experiments d i s c u s s e d below, where-  by s p e c i f i c d e u t e r a t i o n was  combined  with  hydrogen-deuterium  d e c o u p l i n g , would t h e r e f o r e appear to be the f i r s t  example  of t h i s p o t e n t i a l l y powerful technique f o r the s i m p l i f i c a t i o n of n.m.r. s p e c t r a . By the s u b s t i t u t i o n of deuterium f o r hydrogen  i n the  p r e v i o u s l y d e s c r i b e d oxo r e a c t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l  - 85 (22),  I t was  ((83)  and  -  p o s s i b l e to prepare the deuterated  (84))  of the D-arabino-  (44)  analogues  and L - x y l o -  (45)  isomers of l , 5 - a n h y d r o - 4 - d e o x y - h e x i t o l , i n which one of the hydrogens at C-4 C-6  and both of the hydrogens a t t a c h e d at  were r e p l a c e d by deuterium.  In order to reduce  amount of deuterium gas r e q u i r e d the experiment formed on a reduced s c a l e , u s i n g about  the  was  per-  2g of the g l y c a l ,  and the i n t e r n a l volume of the h i g h p r e s s u r e bomb was  re-  duced t o approximately 20 ml by the use of a s m a l l g l a s s l i n e r , c o n t a i n e d i n a hollow metal i n s e r t which c l o s e l y i n s i d e the bomb.  Otherwise,  reaction conditions  were s i m i l a r t o those d e s c r i b e d p r e v i o u s l y .  After  OH  (84)  c a t a l y s t , and d e a c e t y l a t l o n w i t h methanolic  o x i d e , a syrupy product was  removal  OH  (83)  of  fitted  ..  sodium meth-  obtained whose i n f r a r e d  showed a b s o r p t i o n i n the r e g i o n of 2200-2300 cm"  1  spectrum (C-D  stretching).  Chromatography on paper r e v e a l e d two main com-  ponents w i t h R  F  values corresponding to those of the normal  anhydrodeoxyhexitols  (44)  and  (45)J  these were separated on a  -86p r e p a r a t i v e s c a l e as d e s c r i b e d p r e v i o u s l y .  The two  g r a p h l c a l l y pure'fcomponents which were obtained had r o t a t i o n s of -11°  (R  = 0.46)  p  and  -45°  (R  (-42°) very s i m i l a r to those of the The two  The  formed a c r y -  s t a l l i n e a c e t a t e w i t h m e l t i n g p o i n t (80-82°) and  d e r i v a t i v e of (45).  specific  = 0.40).  p  slower-moving, more l e v o r o t a t o r y of the two  rotation  chromato-  specific  corresponding  f r a c t i o n s were t h e r e f o r e  a nhydro-4-deoxy-D-a ra b ino-hex i t o1-4,6,6-H —  2  anhydro-4-deoxy-L-xylo-hexltol-4,6,6-Hg  2  (83)  and  1,5-  1,5-  (84).  The n;m.r. s p e c t r a of the deuterated isomers, measured i n deuterium  oxide s o l u t i o n at 60 Mc/s,  showed i n both  cases  a n t i c i p a t e d s e p a r a t i o n of the r i n g hydrogen s i g n a l s i n t o a low f i e l d m u l t i p l e t of r e l a t i v e i n t e n s i t y 6, and a s i g n a l at  h i g h e r f i e l d corresponding to the one hydrogen attached"  at  C-4,  two  thereby p r o v i d i n g a d d i t i o n a l c o n f i r m a t i o n t h a t the  components separated from the r e a c t i o n were (83)  (84).  The chemical s h i f t s of the C-4  hydrogens ( F i g u r e 2)  are of p a r t i c u l a r i n t e r e s t , i n t h a t they can be  interpreted  as p r o v i d i n g i n f o r m a t i o n on the mode of a d d i t i o n of monoxide and hydrogen to the double bond of D-xylal.  and  carbon  3,4-di-O-acetyl-  I t has a l r e a d y been shown, on the b a s i s of the  ~~  123  evidence obtained by Lemieux and co-workers analogy with the f u l l y  assigned spectrum  that the e q u a t o r i a l hydrogen at C-4 xylo-hexitol  (45)  resonates around 8  , and a l s o by  of methyl c h a l c o s i d e  of 1,5-anhydro-4-deoxy-L=2.0  ppm,  whereas the  b  5  1  10 c/s  Decoupled  Oecoupled  CC^OH  2.0  _L  1.5 ppm(6)  2.0  1.5 ppm (8)  Nmr Spectra (H 4) of Deuterated Hexitols Figure 2  - 87 chemical s h i f t  -  of the a x i a l hydrogen  i s about 1.5  f o r e i t can be assumed that the s i n g l e C-4 (84),  the d e u t e r a t e d analogue of ( 4 5 ) ,  T h i s assumption  the s i g n a l at  a t about  8  =2.0  ppm  and consequently  i s i n an a x i a l o r i e n t a t i o n  (85).  i s supported by the f a c t that the width of  8  = 2.0 ppm  a x i a l hydrogen at C-4 hydrogens  There-  proton s i g n a l of  ( F i g u r e 2A) i s due to an e q u a t o r i a l hydrogen, the deuterium atom at C-4  ppm.  at C-3  i s o n l y about 9 e/s; a s i n g l e  would be coupled w i t h the two  and C - 5 ,  and would t h e r e f o r e have a band  width of the o r d e r of 20 c / s . .  "  Most c o n v i n c i n g evidence f o r the e q u a t o r i a l of  was  p r o v i d e d by the deuterium-decoupled  (85),  a l s o measured i n deuterium oxide s o l u t i o n .  i n the normal spectrum the c o u p l i n g of  with  axial  orientation  spectrum of Whereas  ( F i g u r e 2A), l i n e s r e s u l t i n g and Hp.- were broadened  from  by a d d i t i o n a l  c o u p l i n g w i t h the gem-deuterium atom, and an u n r e s o l v e d 'envelope' was  observed, deuterium-hydrogen  spin decoupling  e f f e c t i v e l y r e s o l v e d the s i g n a l i n t o a s h a r p l y - d e f i n e d q u a r t e t  - 88 (Figure 2B), r e s u l t i n g from the s p l i t t i n g of  (by H^ o r a  H^ ) i n t o a doublet, which was f u r t h e r s p l i t by t h e other g  The two c o u p l i n g constants of 2 . 3 and  a x i a l hydrogen.  5 . 1 c/s which f i t t h i s observed s p l i t t i n g p a t t e r n c o u l d o n l y be accounted  f o r by the f a c t that  was I n a gauche  r e l a t i o n s h i p t o the two a x i a l hydrogens a t C-3 and C - 5 . Hence the deuterium a t t a c h e d a t C-4 and the CDgOH group a t t a c h e d a t C-5 were c i s , and the deuterated anhydrodeoxyhexltol  (85) must have been formed by a c i s a d d i t i o n t o  the double bond o f 3 * 4 - d i - 0 - a c e t y l ~ I ) - x y l a l .  T h i s evidence  f o r c i s a d d i t i o n i n the oxo r e a c t i o n o f g l y c a l s t h e r e f o r e , supports p r e v i o u s experimental evidence o b t a i n e d w i t h other, 29 30 , and i s compatible w i t h c urrrreennttll y 1  u n s a t u r a t e d compounds  a c c e p t a b l e t h e o r i e s of the mechanism of t h i s  reaction  17,18  which were d i s c u s s e d i n the General Introduction.', On t h i s evidence i t was supposed t h a t the i s o m e r i c d e u t e r a t e d anhydrodeoxyhexitol  (83) must a l s o have the  deuterium atom a t C-4 and t h e -CDgOH group a t C-5 i n c i s relationship  (86) I indeed, the chemical  CDOH  s h i f t o f the s i n g l e proton a t C - 4 , 8 - 1.55 ppm* c o u l d w e l l be a s s i g n e d t o an a x i a l hydrogen as i n (87)•  However the h i g h f i e l d  of the spectrum isomer-  o f the normal  portion D-arabino-  ( 4 4 ) , ( F i g u r e 1 C ) , d i d not permit the assignment o f  chemical s h i f t s t o the i n d i v i d u a l hydrogens a t C - 4 ; furthermore,  - 89 the width of the C-4  s i g n a l (Figure 2C)  i s much l e s s than  would be a n t i c i p a t e d f o r an a x i a l hydrogen coupled  a x i a l hydrogen at C-3 as i n (87)• (83)  The  which was  (Figure 2D)  splitting  p a t t e r n of the C-4  r e v e a l e d on hydrogen-deuterium  showed a b a r e l y r e s o l v e d t r i p l e t .  c o u p l i n g constants at C-3  and an e q u a t o r i a l hydrogen at  and C-5  of  with,the two  must be very  s m a l l , and  adjacent  with  an  C-5,  hydrogen i n decoupling Thus the hydrogens  on the b a s i s of  127 Karplus'  parameters  angles between  t h i s i n d i c a t e d that the  and H , and  removed from 90°•  for  (83).  Anhydrodeoxyheptitols from In 1957  3,4,6-Tri-CUacetyl-D-galactal  Rosenthal and Read  3,4,6-tri-O-acetyl-D-galactal hydrogen under oxo  were both not f a r  These data were not c o n s i s t e n t with a  normal c h a i r form (87) B.  and  dihedral  conditions.  (40)  d e s c r i b e d the r e a c t i o n of with carbon monoxide and  Following  d e a c e t y l a t i o n of  the c a t a l y s t - f r e e r e a c t i o n product, one compound, m.p. 158o p —1 _o 159 » LPdrj+38 , was i s o l a t e d by c e l l u l o s e column chromatography  - 90 which, from i t s e m p i r i c a l formula  and those o f i t s c r y s t a l l i n e  benzoyl and p - n i t r o b e n z o y l d e r i v a t i v e s , gave i n d i c a t i o n t h a t a hydroxymethyl group had been added t o the double bond o f the g l y c a l during the course of the oxo r e a c t i o n .  Prom a  study of the o x i d a t i o n and o v e r - o x i d a t i o n of t h i s product .  132 by p e r i o d a t e  , r e s u l t i n g i n the t o t a l consumption o f 6  moles of oxidant and the l i b e r a t i o n o f 2 moles of formic a c i d and one o f formaldehyde, i t was concluded  t h a t the  hydroxymethyl group had probably added at C-2 o f the g l y c a l , g i v i n g r i s e t o the branched c h a i n carbohydrate (88) of unknown c o n f i g u r a t i o n at C - 2 . The work d e s c r i b e d i n t h i s  AcO  (88)  (40)  s e c t i o n comprises  a f u r t h e r i n v e s t i g a t i o n o f the oxo r e a c t i o n  of 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l . (i)  Reaction Conditions  (a)  3,4,6-Tri-O-acetyl-D-Galaetal The  Tlpson  133  (4o)  f i r s t recorded p r e p a r a t i o n o f (40) by Levene and used the procedure  "31  of F i s c h e r -  3  } other m o d i f i c a t i o n s  - 91 134 have been d e s c r i b e d by Bates and co-workers , and by Overend 42 and co-workers . In t h i s work the convenient procedure 45 of H e l f e r l c h and co-workers of  was  3 j 4 , 6 - t r i - 0 - a c e t y l - D - g a l a c t a i , and one  good o v e r a l l y i e l d g l y c a l was product.  (76$  from D-galactose  However, o t h e r attempts  (18))  of pure reaction  at p u r i f i c a t i o n ,  following  CH OAc 2  2  —O  Ac 0/H 2  QH  one o c c a s i o n a  obtained on d i s t i l l a t i o n of the crude  CH OH HQ  used f o r the p r e p a r a t i o n  > > H  0 H  2.  +  —O,  AcO  P/Br /H 0 2  Zn/AcOH  > VOAc Br OAc  2  (18)  55  (40)  (89)  p r e p a r a t i o n by the same procedure, r e s u l t e d i n r a p i d composition w i t h e v o l u t i o n of a c e t i c a c i d when the  de-  crude  product, known to c o n t a i n a h i g h p r o p o r t i o n of the g l y c a l , was  heated under vacuum.  L i t t l e improvement was  obtained  45 when the procedure  of H e l f e r i c h  was  m o d i f i e d by p r e l i m i n a r y  i s o l a t i o n and p u r i f i c a t i o n of the i n t e r m e d i a t e 2 , 3 , 4 , 6 - t e t r a 0 - a c e t y l - o c - D - g a l a c t o s y l bromide ( 8 9 ) . t i o n r e s u l t e d i n decomposition,  i t was  In cases where  distilla-  found, p o s s i b l e to e f f e c t  a p u r i f i c a t i o n of small amounts of the crude product by chromato graphy on a column of F l o r i s i l .  :  - 92 (b)  R e a c t i o n C o n d i t i o n s and Conditions  + 2H  Product I s o l a t i o n  employed f o r the r e a c t i o n of 3 , 4 , 6 - t r i -  O-acetyl-D-galactal (CO  -  (4o)  w i t h 3 moles of s y n t h e s i s  gas  ) were i n g e n e r a l s i m i l a r to those used by  63 Rosenthal and Read  , and to those p r e v i o u s l y d e s c r i b e d  i n S e c t i o n A f o r the corresponding acetyl-D-xylal g l y c a l s has  (22).  r e a c t i o n of 3 , 4 - d i - O -  Previous work on the oxo  r e a c t i o n of  i n d i c a t e d that the a c e t y l a t e d hexals are some-  what l e s s r e a c t i v e than the p e n t a l d e r i v a t i v e s , t h e r e f o r e a s l i g h t l y h i g h e r r e a c t i o n temperature ( 1 3 5 ° ) was Reaction  products  were separated  used.  from c a t a l y s t and  i s o l a t e d as p r e v i o u s l y d e s c r i b e d i n S e c t i o n A, to g i v e a syrupy product  whose i n f r a r e d spectrum showed that a d d i t i o n  to the double bond was  complete (absence of G=C  v i b r a t i o n s around 1640  c m ) , and which showed a - 1  band of moderate i n t e n s i t y at 3^00  cm . -1  The  t h e r e f o r e compatible with the presence of one alcohols.  No attempt was  stretching hydroxyl  spectrum  was  or more sugar  made to f r a c t i o n a t e the  product  i n the a c e t y l a t e d form, as t h i n l a y e r chromatography showed a mixture of components which was product  was  methoxide was  72  not w e l l r e s o l v e d .  The  then d e a c e t y l a t e d w i t h methanollc sodium to g i v e a p a r t i a l l y c r y s t a l l i n e m a t e r i a l which  examined by paper chromatography, u s i n g the p r e v i o u s l y  d e s c r i b e d s o l v e n t system of w a t e r - s a t u r a t e d  1-butanol c o n t a i n i n g  - 93 5$ e t h a n o l .  When development  -  of the chromatogram was i n -  t e r r u p t e d at the p o i n t where the s o l v e n t f r o n t was  near the  lower edge, only one major zone of low m o b i l i t y was on s p r a y i n g w i t h p e r i o d a t e - S c h i f f reagent''' . 3  apparent  However on  d e v e l o p i n g the chromatograms f o r i n c r e a s i n g l y l o n g e r p e r i o d s the a p p a r e n t l y homogeneous main zone became r e s o l v e d two d i s t i n c t components, which a f t e r development  into  f o r about  60 hours at room temperature were near the l e a d i n g edge of the paper and s u f f i c i e n t l y s e p a r a t e d to j u s t i f y an attempted f r a c t i o n a t i o n on a p r e p a r a t i v e s c a l e . p o r t i o n of the d e a c e t y l a t e d product was  F r a c t i o n a t i o n of a c a r r i e d out by  e s s e n t i a l l y the same procedure used t o s e p a r a t e the anhydrod e o x y h e x i t o l s d e r i v e d from 3 , 4 - d i - O - a c e t y l - D - x y l a l A).  (Section  Recovery o f the two f r a c t i o n s , which were present i n  approximately equal amounts, r e p r e s e n t e d about 75$ of the m a t e r i a l a p p l i e d t o the chromatograms.  For the purposes  of subsequent d i s c u s s i o n the f a s t e r - m o v i n g of the two  will  be r e f e r r e d t o as F r a c t i o n A, and the slower as F r a c t i o n (ii)  B.  C h a r a c t e r i s a t i o n of F r a c t i o n s A and B —  1  1  1  u  Rp v a l u e s of the two f r a c t i o n s were measured on paper w i t h the same s o l v e n t system used f o r t h e i r s e p a r a t i o n , conf i r m i n g t h a t each was  c h r o m a t o g r a p h i c a l l y pure.  Both f r a c -  t i o n s were o b t a i n e d i n c r y s t a l l i n e form, and gave elemental analyses  c o r r e s p o n d i n g to the a n t i c i p a t e d e m p i r i c a l formula  ) r e q u i r e d by the a d d i t i o n of a hydroxymethyl group to the g l y c a l double bond.  in. p.  R  (a)  r  p  -, (b) [ocJ D  Fraction A  158-9°  0.24  24°  Fraction B  168°  0.21  68°  (a)  i n w a t e r - s a t u r a t e d 1-butanol -f 5$ ethanol a t room temperature  (b)  i n water a t room temperature  F r a c t i o n s A and B were both c h a r a c t e r i s e d as c r y s t a l l i n e p-nitrobenzoyl  d e r i v a t i v e s , - prepared by r e a c t i o n w i t h  82 p-nitrobenzoyl  chloride i n pyridine  , whose analyses  compatible w i t h the e s t e r i f i c a t i o n of f o u r h y d r o x y l  were  groups  i n each case. (iii)  Structures  of F r a c t i o n s A and B  I t was p o s s i b l e t o determine the m o l e c u l a r s t r u c t u r e s of F r a c t i o n s A and B by a s i m i l a r approach t o that used i n determining the s t r u c t u r e s o f anhydrodeoxyhexitols I and I I (Section A).  However, the problem of determining the a b s o l u t  stereochemistry  o f the two F r a c t i o n s was not amenable t o s o l u  t i o n by c l a s s i c a l methods. In view of the e a r l i e r I n v e s t i g a t i o n c a r r i e d out by Rosenthal and Read^  3  on the i d e n t i t y of the s i n g l e p o l y o l ,  - 95 i s o l a t e d from the oxo r e a c t i o n products of 3 j 4 , 6 - t r l - 0 - a c e t y l D - g a l a c t a l , which was thought to have a branched-chain s t r u c ture  (88),  i t was of p a r t i c u l a r i n t e r e s t t o e s t a b l i s h the  configurations reaction.  of F r a c t i o n s A and B obtained from the same  As w i t h the h e x i t o l s ( F r a c t i o n s I and I I ) d e r i v e d  from the oxo r e a c t i o n of 3 , 4 - d i - 0 - a c e t y l - D - X y l a l > - ^ i t a g a i n assumed that f o u r isomeric  compounds, (90)  was  -., ( 9 3 ) ,  were t h e o r e t i c a l p o s s i b l e by the a d d i t i o n of a hydrogen atom and a hydroxymethyl.group at e i t h e r end of the double bond of (40). C o n s i d e r a t i o n  CI-tpH HO  structures  CH^DH  CH OH  CH OH 2  \—0  2  -OXH^H  HQ  (90)  :..  of these four- p o s s i b l e  HQ  (92)  (91)  CHJOH  —O,  (93)  2  I  CH OH 2  CH  2  CH OH 2  H-*C—O—C-H  I  CH^H  (94)  T  CH^DH  CH QH C H 2  2  H-C— O-C-H £H OH 2  ih^OH  (95)  CH^H^  CH OH 2  H-G-O-CH-C-H C^OH  Ch^OH  (96)  shows t h a t the argument p r e v i o u s l y a p p l i e d i n d e c i d i n g between branched and s t r a i g h t - c h a i n s t r u c t u r e s f o r F r a c t i o n s I and I I was e q u a l l y v a l i d i n - t h i s case*  Periodate  cleavage  *  .96  ~  of the o c - g l y c o l group o f any one o f the f o u r (90) -  polyols  ( 9 3 ) and r e d u c t i o n  isomeric  o f the d i a l d e h y d e so  formed would a f f o r d a t e t r o l e t h e r which would b e ^ ' o ^ i c f i l l y a c t i v e , having one asymmetric carbon atom (*) from one o f t h e s t r a i g h t c h a i n h e p t i t o l s  ( 9 0 ) o r ( 9 1 ) , but  would be devoid o f asymmetry and t h e r e f o r e active (92)  ( 9 6 ) i f derived  and  i f formed  optically in-  from e i t h e r o f t h e branched Isomers  ( 9 3 ) .  When F r a c t i o n s  A and B were s e p a r a t e l y  oxidised  w i t h an excess of p e r i o d i c a c i d , and the r e s u l t i n g d i a l d e h y d e s , a f t e r n e u t r a l i s a t i o n o f the r e a c t i o n medium, were reduced i n aqueous s o l u t i o n w i t h sodium b o r o h y d r i d e , syrupy products were obtained a f t e r working up t h e r e a c t i o n  i n the u s u a l  way which had equal and o p p o s i t e r o t a t i o n s ; t h e t e t r o l e t h e r from F r a c t i o n A was d e x t r o r o t a t o r y  ( [pilp  and  ( [ocj^ - 2 3 ° ) .  that  from F r a c t i o n B was l e v o r o t a t o r y  C o n f i r m a t i o n o f the s t r u c t u r e s  of the t e t r o l e t h e r s thus  obtained was p r o v i d e d by t h e i r n.m.r. s p e c t r a , In deuterium oxide s o l u t i o n . showed a m u l t i p l e t  + 2 1 ° ) ,  measured  These were i d e n t i c a l and  a t lower f i e l d {8=  ( 8 = 3 . 5 0 - 3 . 8 5 ppm) 1 . 4 7 - 1 . 0 2 ppm) which  and  a group a t h i g h e r f i e l d  had  the appearance o f a q u a r t e t o f l i n e s .  The r e l a t i v e  i n t e n s i t i e s o f t h e two groups of n o n - h y d r o x y l i c hydrogen s i g n a l s were i n the r a t i o o f 1 0 J 2 , c o n s i s t e n t  w i t h the 2 -  deoxy-3-0-(l,3-dihydroxy-2-propyl)-glycero-tetritol  structure  - 97 of t e t r o l ethers (94)  (95),  and  of the t e t r o l ether ( 9 6 ) ,  but not w i t h the s t r u c t u r e  which would have been formed  e i t h e r F r a c t i o n s A or B been branched as  (96)  c o n t a i n s o n l y one hydrogen  had  chain structures,  a t t a c h e d to a carbon  atom without an oc-oxygen f u n c t i o n , and e l e v e n o t h e r non-  79 h y d r o x y l i c hydrogens which would resonate at lower  field  Apart from the r e l a t i v e i n t e n s i t i e s of the low and h i g h f i e l d groups of s i g n a l s , the c l o s e s i m i l a r i t y between the s p e c t r a of the t e t r o l ethers obtained from these r e a c t i o n s and those of the enantiomeric glycero-tetritols  (48) and  2-deoxy-3-0-(2-hydroxyethyl)-  (49) p r e v i o u s l y d e r i v e d from  the s t r a i g h t c h a i n anhydrodeoxyhexitols worthy of note.  (44) and  (45) i s  The t e t r o l ethers from F r a c t i o n s A and B  were c h a r a c t e r i s e d as the t e t r a - O - p - n i t r o b e n z o y l d e r i v a t i v e s , prepared and I s o l a t e d In the u s u a l way. o  The d e r i v a t i v e of  Q  F r a c t i o n A, m.p.  150-151 ,  [ 0 ^ + 23  , had an i n f r a r e d  spec-  trum i d e n t i c a l w i t h that prepared from F r a c t i o n B, which had m.p.  150-151°,  G?^  -23°,  these data p r o v i d i n g  further  evidence f o r the enantiomeric nature of the two t e t r o l e t h e r s . Apart from the evidence thus obtained from t h e i r  de-  g r a d a t i o n s t o o p t i c a l l y a c t i v e compounds, the n.m.r. s p e c t r a of the two p o l y o l s A and B  ( F i g u r e 3)  were" a l s o  indicative  of the f a c t that both had s t r a i g h t c h a i n , r a t h e r than chain structures.  branched  Measured i n deuterium oxide s o l u t i o n , the  s p e c t r a of both A and B showed s e p a r a t i o n of s i g n a l s i n t o a  FractionI  2X)  Fraction JT  1.0 Ppm(S)  4.0  3.0  Nmr Spectra of Anhydrodeoxyheptitols  Figure 3  2.0  J  IX) ppm (8)  -  98 -  h i g h e r f i e l d group w i t h i n the r e g i o n of S = 1.3 (area= 2) 8 around  - 2.1  ppm  and a complex m u l t i p l e t w i t h a r e l a t i v e area of 8=  3.2  - 4.3  ppm.  The observed i n t e n s i t i e s were  compatible o n l y w i t h s t r u c t u r e s  (90)  s o l u t i o n e i t h e r of the branched  chain polyols  and  (91),  as i n D^O (92)  (93)  and  would have o n l y a s i n g l e hydrogen (cJjH-C) r e s o n a t i n g i n the h i g h e r f i e l d r e g i o n , and nine other l e s s s h i e l d e d gens.  N e i t h e r spectrum  ( F i g u r e 3)  showed any  spin-spin  m u l t i p l i c i t i e s of v a l u e i n d i s t i n g u i s h i n g between the s t r u c t u r e s (90)  and  hydro-  two  (91).  On t h i s evidence i t c o u l d be concluded t h a t both F r a c t i o n A and F r a c t i o n B were  2,6-anhydro-3-deoxy-heptitols,  and t h e r e f o r e d i f f e r e d o n l y i n c o n f i g u r a t i o n a t C - 2 . one of the two heptitol  (91),  f r a c t i o n s was  Thus  2,6-a nhydro-3-dteoxy-D-ga l a c to -  forming the t e t r o l ether 2 - d e o x y - 3 - 0 - ( 1 , 3 -  dihydroxy-2-propyl)-L-glycero-tetritol  (95)  on cleavage w i t h  p e r i o d a t e and r e d u c t i o n w i t h sodium b o r o h y d r i d e , and o t h e r f r a c t i o n was  the corresponding D-talo-lsomer  which the t e t r o l e t h e r (94) obtained.  the  (90),  from  having the D - c o n f i g u r a t i o n was  -  99  "  H' i _  0  - C H ,  (94) (90)  (91) (iv) (a)  S t e r e o c h e m i s t r y of F r a c t i o n s A and B P e r i o d a t e Consumption and  Acetalation  Determination of the amount of p e r i o d a t e i o n coni  sumed by both F r a c t i o n s A and B, by the p r e v i o u s l y d e s c r i b e d s p e c t r o p h o t o m e t r y method  76  ,  •  •  |  confirmed the presence i n each  compound of one c x - g l y c o l group, one molar e q u i v a l e n t of p e r i o d a t e i o n r e a c t i n g i n each case.  The r a t e s of r e a c t i o n  w i t h p e r i o d a t e i o n r e l a t i v e to those p r e v i o u s l y f o r the two anhydrodeoxyhexitols (44)  and  (45)  determined were of i n -  t e r e s t , the r e a c t i o n b e i n g much f a s t e r f o r the two d e o x y h e p t i t o l s A and B than f o r (44) t r a n s arrangement  and  (45),  anhydro-  i n which a  of secondary h y d r o x y l groups was  present.  T h i s i s c l e a r l y shown i n the t a b l e on the next page, which compares the mole f r a c t i o n of p e r i o d a t e i o n consumed a g a i n s t time f o r anhydrodeoxyhexitol (45)  and a n h y d r o d e o x y h e p t i t o l B,  - 100 which were r e a c t e d Time 1  min. 47  O.63  (a)  -  under I d e n t i c a l  conditions.  h r s . 3 h r s . 10.5  min. 1.5  h r s . 17  0.97 0.40  Moles of Periodate  0.59  0.88  0.95  Ion Consumed per Mole of S u b s t r a t e  2 , 6 - A n h y d r o - 3 - d e o x y - h e p t i t o l ( F r a c t i o n B)J  for  (a)  (b)  1,5-Anhydro«4-deoxy-L-xylo-hexitol  (45).  exact mechanism by which the carbon-carbon bond  c o n n e c t i n g the adjacent h y d r o x y l groups of an broken has  hrs.  0.87  00  The  h r s . 24  not been e s t a b l i s h e d  c o n c l u s i v e l y , but  e s t e r s t r u c t u r e such as  (97), f i r s t  i s generally  to be ah i n t e r m e d i a t e  considered  oc-glycol i s  proposed by  a cyclic Criegee "^, 1  i n the  proc-  74 ess  .  The  w e l l known d i f f e r e n c e i n r a t e of  -C—0. -C—Or  :IO H 4  periodate  3  (97) o x i d a t i o n between c i s and to a six-membered,ring  I36  trans has  o c - g l y c o l groups a t t a c h e d  been r a t i o n a l i s e d oh  con-  137 formatiohal  grounds by Hoheymah and  observed i n the r a t e of p e r i o d a t e  Shaw  .  Variations  consumption of a number  o f pyranoside d e r i v a t i v e s , i n which only one  o c - g l y c o l group  - 101 of known conformation was  -  a v a i l a b l e f o r o x i d a t i o n , were con-  s i s t e n t w i t h the f a c t t h a t the r a t e was r e l a t i v e ease of formation as  (97).  dependent on  of a c y c l i c i n t e r m e d i a t e  Attachment of such a 5-membered c y c l i c  onto a pyranoid  r i n g would r e q u i r e the C-0  o c - g l y c o l group t o be c o n s t r a i n e d  such  structure  bonds of  (99),  as the two  diols.  trans-  In the l a t t e r case  carbon atoms of the d i o l s y s t i t i are  i n order to b r i n g the two  attached  the  i n t o a g r e a t e r degree of .  c o p l a n a r i t y f o r both c i s - ( a x i a l - e q u a t o r i a l ) ( 9 8 ) and (equatorial-equatorial):(99)  the  rotated  oxygen atoms c l o s e r t o -  g e t h e r , the r i n g becomes more puckered; consequently the...axial  (98)  (99)  a x i a l s u b s t i t u e n t s on the r i n g are brought c l o s e r and  considerable  repulsions. systems ( 9 8 ) ,  The  energy i s r e q u i r e d to overcome the r e s u l t i n g reverse  applies with c i s (axial-equatorial)  where a s i m i l a r o p e r a t i o n  becoming l e s s puckered, and appreciably  together  changed.  interatomic  r e s u l t s i n the r i n g r e p u l s i o n s are  Formation of a c y c l i c  f o r e proceeds r e a d i l y .  The  intermediate  r a p i d r a t e s of p e r i o d a t e  not there-  oxidation  - 102 of F r a c t i o n s A and B r e l a t i v e to those of anhydrodeoxyhexitols (44)  (45)  and  thus demonstrated  secondary h y d r o x y l groups at C-4  the c i s c o n f i g u r a t i o n of the and C-5  of the two  anhydro-  deoxyheptitols. A s i m i l a r e x p l a n a t i o n f o r the more ready f o r m a t i o n of the O - i s o p r o p y l i d e n e d e r i v a t i v e s of an  oc-glycol  group  s i t u a t e d on a six-membered r i n g when the h y d r o x y l groups are c i s , r a t h e r than t r a n s , has been proposed by Angyal and  138 Macdoiald  .  Here the d i f f e r e n c e i n energy r e q u i r e d t o  assume a g r e a t e r degree of c o p l a n a r i t y f o r the of (98)  and  (99)  —<jj- groups  i s such that under normal c o n d i t i o n s the  O - i s o p r o p y l i d e n e d e r i v a t i v e of a t r a n s d i o l does not I t should be noted, however, that complete the f i v e atoms of the 1 , 3 - d i o x o l a n e d e r i v a t i v e s i s not, as was TOQ nil© formation  .  form.  c o p l a n a r i t y of  type r i n g of O - i s o p r o p y l i d e n e  once supposed,  necessary f o r t h e i r  A d d i t i o n a l evidence f o r the presence of  two a d j a c e n t secondary h y d r o x y l groups h a v i n g a c i s arrangement i n one of the a n h y d r o d e o x y h e p t l t o l s was ready r e a c t i o n w i t h acetone, subsequent the mono-O-isopropylidene  p r o v i d e d by i t s  evidence showing  that  d e r i v a t i v e so formed d i d not gngage  e i t h e r of the primary h y d r o x y l groups  i n the molecule.  The  r e s u l t s o b t a i n e d c o u l d be i n t e r p r e t e d i n terras of the p o s s i b l e s t e r e o c h e m i s t r y a t C-2  of 2,6-#§taydro-3-deoxy-heptitol  B.  - 103 The r e a c t i o n o f F r a c t i o n B w i t h acetone at room  tempera-  t u r e , c a t a l y s e d by a t r a c e o f s u l p h u r i c a c i d , gave an o i l from which t h e r e a c t i o n product was r e a d i l y removed by e x t r a c t i o n . w i t h b o i l i n g carbon t e t r a c h l o r i d e , i n which t h e unreacted p o l y o l was i n s o l u b l e .  The l a t t e r c o u l d then be s u b j e c t e d  to f u r t h e r treatment w i t h a c i d i f i e d acetone, thereby e n a b l i n g the product t o be obtained i n good o v e r a l l y i e l d . s t a l l i n e d e r i v a t i v e , m.p. 1 0 4 - 1 0 5 ° ,  The c r y -  [pcj-p + 12°, gave an e l e -  mental a n a l y s i s i n agreement w i t h the emp|fp.eal formula (G _H,oO ) r e q u i r e d f o r the mono-O-isopropylidene (100)  of a 2,6-anhydro-3-deoxy-heptitol.  derivative  The presence o f  two f r e e h y d r o x y l groups was shown by c o n v e r s i o n o f (100)  (100)  (102)  to a di-0-p4;olysulWi°nyl d e r i v a t i v e  ( 1 0 1 ) , m.p. 135°>.  •  -42°.  I t was then p o s s i b l e t o c o n f i r m that both hydroxy!' groups o f the mono-O-isopropylidene  derivative  a c e t a l formation were primary. derivative  (100) not i n v o l v e d i n  When the d i - O - p - t o l y s u l p h o n y l  (101) was heated i n a s e a l e d tube w i t h sodium  iodide  - .104 i n acetone s o l u t i o n f o r 26 hours at 1 1 8 ° , sodium p-toluenesulphonate which was by f i l t r a t i o n was  the amount of  subsequently i s o l a t e d  e q u i v a l e n t to the replacement of two  tbsy-  l o x y groups by i o d i d e , to g i v e the 1,7-dideoxy- d e r i v a t i v e (102)  (which was  cterisation) . are  not obtained i n s u f f i c i e n t amount f o r c h a r a 1  I t i s w e l l known t h a t primary t o s y l o x y  groups  r e p l a c e d by i o d i d e under these c o n d i t i o n s , whereas those  94 at  secondary p o s i t i o n s are g e n e r a l l y u n r e a c t i v e  .  These  r e a c t i o n s t h e r e f o r e demonstrated the presence of two adjacent secondary h y d r o x y l groups having a c i s r e l a t i o n s h i p , i n a d d i t i o n t o two primary h y d r o x y l s , i n F r a c t i o n B. . In  order t o o b t a i n the s e p a r a t i o n of an amount of  sodium p - t o l u e n e s u l p h o n a t e  e q u i v a l e n t t o the replacement  of both primary t o s y l o x y groups of ( 1 0 1 ) , i t was necessary to  employ a l o n g e r time and a h i g h e r temperature than i s  usual f o r t h i s r e a c t i o n .  However, the f o r m a t i o n of an  a p p r e c i a b l e amount of sodium p-toluenesulphOHate was bbL !  served w i t h i n minutes of the s t a r t of the r e a c t i o n , w h i l e the  temperature was  s t i l l below 1 0 0 ° ,  and i n a separate ex-  periment c a r r i e d out under the same c o n d i t i o n s , but at a temperature of 1 0 0 ° ,  sodium  p-toluenesul^^^^  a f t e r 25 minutes e q u i v a l e n t t o the replacement of one group by i o d i d e . of  I t was  tosyloxy  apparent t h e r e f o r e , t h a t whereas one  the primary t o s y l o x y groups of (101)  w i t h unusual ease, the o t h e r was  was  r e p l a c e d by i o d i d e  replaced with d i f f i c u l t y .  - 105  -  I t has been shown t h a t the p r o x i m i t y  of an a c e t a l r i n g  can render an otherwise r e a c t i v e primary t o s y l o x y group r a t h e r i n e r t to the a c t i o n of sodium i o d i d e . p-tolyls\tlphonyl-D-ga l a c t o s e was  Thus whereas 2 , 6 - d i - 0 -  r e a d i l y converted to  the  6-deoxy-6-iodo- d e r i v a t i v e i n good y i e l d , the r e a c t i o n of the corresponding 3>4-0_-isopropylidene d e r i v a t i v e  (103)  w i t h sodium i o d i d e under i d e n t i c a l c o n d i t i o n s r e s u l t e d i n only 18$  replacement of the primary t o s y l o x y group by i o d i d e  S i m i l a r l y , replacement of the ^primary t o s y l o x y group i n  1,2!  (101) 3,4-di-0-isopropylidene-6-0-p-tolylsulphonyl(104)  r e q u i r e s h e a t i n g w i t h sodium i o d i d e i n acetone f o r 118  36 hours at 125° to  (103)  and  (104)  .  The  s t r u c t u r a l s i m i l a r i t y of  ( 1 0 1 ) , that at 0 - 7 , which r e a c t e d  (101)  i s apparent; hence, by analogy, i t  be concluded t h a t , of the two  one  oc-D-galactose  adjacent  may  primary t o s y l o x y groups of t o the a c e t a l r i n g , was  s l o w l y w i t h sodium i o d i d e at 1 1 8 ° ,  the  and o t h a t the C - l t o s y l o x y group r e a c t e d very r e a d i l y at 100 .  ;  - 106 I t was then of I n t e r e s t of t h e j r e a c t i v e t e r m i n a l be  t o s p e c u l a t e on the l i k e l y  orientation  group o f ( 1 0 1 ) , which must  tosyloxy  (in 2,6-anhydro-3-deoxy-4,5-Q-lsopropyll-  either equatorial  d e n e - l , 7 - d i - 0 - p - t o l y s u l p h o n y l - D - g a J L a e t o _ - h e p t i t o l (1^05)) o r axial  ( i n the corresponding d e r i v a t i v e  taj|6-  configuration).  (106) having the  Evidence i s a v a i l a b l e which demonstrates t h a t an axially-disposed  primary t o s y l o x y  iodide with greater  group w i l l r e a c t w i t h sodium  ease than an e q u a t o r i a l group, when both -i  are i n s i m i l a r environments  42 .  The b i c y c l i c d i a c e t a l s o f  h e x i t o l s , by c i s f u s i o n of ifao six-membered r i n g s , structures  p o s s e s s i n g two t e r m i n a l  give  hydroxymethyl groups  which can be a x i a l or e q u a t o r i a l , depending on the c o n f i g u r a t i o n o f the parent h e x i t o l .  Thus 2,4:3,5-di-0-methylene-D-  128  ~~  glucitol  ( 1 0 7 ) , i n the p r e f e r r e d  terminal  C-6 group a x i a l and the C - l group e q u a t o r i a l .  has  conformation  , has the It  been shown t h a t , on r e a c t i o n o f the l , 6 - d i - 0 - p - t o l y l -  s u l p h o n y l d e r i v a t i v e o f (107) w i t h sodium i o d i d e , the a x i a l  - 107  -  (107) tosyloxy  group at C-6 was 143  replaced  more r e a d i l y than  S i m i l a r l y , the replacement  the  e q u a t o r i a l C - l group  .  i o d i d e of the t o s y l o x y  groups of 2,4:3,5-di-0-methylene-  1,6-dl-O-p-tolylsulphonyl-L-idltol ol44 ~~ v e r y slow at 100  (both e q u a t o r i a l )  , whereas w i t h the c o r r e s p o n d i n g  v a t i v e o f D-mannitol, both ( a x i a l ) t o s y l o x y  groups  by  was deri-  reacted  145~ rapidly that  .  (101)  orientation  On  may  the b a s i s of these data, i t was have had  the 0-1  tosyloxy  considered  group i n an a x i a l  ( 1 0 6 ) , i n which case F r a c t i o n B would be  anhydro-3-deoxy-B-talo-heptitol (90). showed t h a t t h i s s p e c u l a t i o n was,  2,6-  Subsequent evidence  i n fact,, c o r r e c t . . I t  would have been of i n t e r e s t to compare the  same r e a c t i o n s  of the c o r r e s p o n d i n g d e r i v a t i v e s of F r a c t i o n Aj however, t h i s compound, being s p a r i n g l y s o l u b l e In acetone, d i d  not  form an O - i s o p r o p y l i d e n e d e r i v a t i v e In s u f f i c i e n t amounts f o r c h a r a c t e r i s a t i o n and  derivatisation. .  1  - 108 !(b)  S t e r e o c h e m i s t r y at  0-2  Attempts were made to s o l v e the problem of the f i g u r a t i o n s of the enantiomeric f r o m ' F r a c t i o n s A and B, chemistry of the two  t e t r o l ethers  con  obtained  (and hence the a b s o l u t e s t e r e o -  a n h y d r o d e o x y h e p t i t o l s ) , by the  prepara-  t i o n of one.of them from a s u i t a b l e s t r u c t u r e whose c o n f i g u r a t i o n at the p o t e n t i a l asymmetric c e n t r e (0-3 e t h e r s ) was  known (a procedure  of the  tetrol  which had p r e v i o u s l y been  s u c c e s s f u l i n p r o v i n g the s t r u c t u r e s of the anhydrodeoxyhexitols  (44)  and  (45)  (59)).  by c o r r e l a t i o n w i t h  By  the  same approach, p o s s i b l e s t r u c t u r e s which would a f f o r d a 2-deoxy-3-0-(l,3-dihydroxy-2-propyl)-glycero-tetritol  (109)  were! (a)  2,6-anhydro-3-deoxy-heptitols  A and B, (b)  (108)  other  than F r a c t i o n s  and  3,6-anhydro-2-deoxy-heptitols  both by p e r i o d a t e cleavage sequent r e d u c t i o n .  (11©),  of the C-4  - C-5  bond and  At the time t h i s i n v e s t i g a t i o n  sub-  was  CHPH  59  CHOH  2.  (108)  (109)  (no)  I  - 109  -  undertaken no other compounds of the former type (108)  were  a v a i l a b l e whose s t e r e o c h e m i s t r y had been e s t a b l i s h e d ,  and 3,6-  a search of the l i t e r a t u r e f a i l e d t o r e v e a l any known anhydro-2-deoxy-heptitols  (Hip).  However, i t was c o n s i d e r e d  that a p o s s i b l e s y n t h e t i c route t o the l a t t e r type of structure  (110)  would be the a p p l i c a t i o n t o a 2,5-anhydro-  hexose ( i l l ) of a known procedure  (the  Fischer-Sowden  146, nitromethane  synthesis  gous 2-deoxy-aldoses,  ) f o r the p r e p a r a t i o n the product  (112)  of homolo-  on r e d u c t i o n  then  a f f o r d i n g the r e q u i r e d 3 , 6 - a n h y d r o - 2 - d e o x y - h e p t i t o l  (llO),  whose c o n f i g u r a t i o n at C-3  of  would be the same as C-2  (ill)J  thus  OHO CHO ChW I  AH \  IOH  . 1  CHOH\ CHOHy  2  Ahl-^  F i s c h e r - 1,  • S o w d e n  >GHOH\ GHOH/  inpH  AH^OH  (111)  (112)  (°)  Attempted  60  A Reduction.  Syntheses  —>  (no)  >  (io ) 9  of 3,6-Anhdyro-2-deoxy-heptltols  (110)  2,5-  Of the 2,5-anhydro-hexoses, the best known i s  anhydro-D-mannose ( c h i t o s e ) ( 1 1 5 ) > an amorphous m a t e r i a l , 147 2,5-anhydro-D-mannose has been known f o r many years  1  , but  only comparatively r e c e n t l y has i t s s t r u c t u r e been e s t a b l i s h e d  - 110 148,149 beyond doubt  '  , c o n f i r m i n g the p r e v i o u s c o n c l u s i o n s  of Levlne and LaForge  . The formation o f (115) by t h e  n i t r o u s a c i d deamlnatlon o f 2-amino-2-deoxy-D-glucose  (113)  i n v o l v e s an i n v e r s i o n i n c o n f i g u r a t i o n a t C-2, and i s cons i d e r e d t o proceed v i a an i n t e r m e d i a t e diazonium s a l t 95 (114)  J subsequent e l i m i n a t i o n i s accompanied by rearward  a t t a c k o f the r i n g oxygen a t C-2, r e s u l t i n g i n rearrangement of a s i x - t o a five-membered r i n g .  2,5-Anhydro-D-glucose  6l  CHO (115)  ( 1 1 7 ) , the eplmer o f (115).,- i s a l s o known and has been obt a i n e d by t h e analogous deamlnatlon o f 2-amino-2-deoxy-Dmannose h y d r o c h l o r i d e  (.116) by the a c t i o n o f mercuric  151  oxide""''"", again w i t h i n v e r s i o n a t C-2  CHf)H  CHpH HCI H,OH (116)  (117)  62  - iii  -  Though l e s s - r e a d i l y a v a i l a b l e , 2,5-anhydro-D-glucose (117) was s e l e c t e d as being a more s u i t a b l e s t a r t i n g m a t e r i a l f o r the attempted p r e p a r a t i o n of a 3,6-anhydro-2-deoxyheptitol (a)  (110) than i t s epimer (115)  f o r two reasons:  i t i s r e p o r t e d t o be a h i g h l y - c r y s t a l l i n e  whereas (115) i s an i l l - d e f i n e d syrup, and  (b)  solid, the p r e -  p a r a t i o n of i t s p r e c u r s o r , 2-amino-2-deoxy-D-mannose hydrochloride 63,  ( l l 6 ) from D-arabinose  (118), a c c o r d i n g t o Equation  would a f f o r d a s e r i e s of i n t e r m e d i a t e compounds  ((119),  (120) and (121)) which would p r o v i d e u s e f u l models f o r f o l l o w i n g the subsequently  planned  c o n v e r s i o n of (117) t o  3,6-anhydro-2-deoxy-D-manno-heptltol (124), a l s o v i a the nitre-methane  s y n t h e s i s f o r 2-deoxy-sugars (Equation 64). 152  The  p r e p a r a t i o n , d e s c r i b e d by Sowden and O f t e d a h l  of 2-amino-2-deoxy-D-mannose h y d r o c h l o r i d e ( l l 6 ) from Darabinose  (118), by way of D - a r a b i n o - t e t r a a c e t o x y - l - n i t r o -  1-hexene (121) (Equation 63) proceeded smoothly, w i t h format i o n of h i g h l y - c r y s t a l l i n e i n t e r m e d i a t e s .  However, the  attempted c o n v e r s i o n of ( l l 6 ) t o 2,5-anhydro-D-glucose  (117),  151 by  the method of Levine  i n v o l v i n g the a c t i o n of mercuric  oxide, d i d not g i v e the a n t i c i p a t e d c r y s t a l l i n e anhydrosugar  (117)5 an amorphous brown s o l i d was o b t a i n e d which  c o u l d not be p u r i f i e d .  - 112 A t t e n t i o n was then turned to the use of the more a c c e s s i b l e 2,5-anhydro-D-mannose the method of Grant  15 3  CH N0 2  , who i n v e s t i g a t e d the s t a b i l i t y of  HO-C-H  2  hkC-OAc  H-C-OH  H-C-OAc  H-C-OAc  wHOAc  ih^OAc  A H^OH  2  (118)  AcO-C-H  AcO-C-H H-C-OAcf  HOH  4 H 0H "  AcO-C-H  H-C-OH  +  OH  CKNO^  2  H-C-OAc  HO-C-H  -OH  H-C-OH  h^N0  HO-C-H  HO-C-H-  H-C-OH"  CHJM  2  H-C-OH  CHO  (115); t h i s was made by  —  (119)  (120)  63  CH^NC^  CH  H-C-NH-€Ac A:'r-HN-C—H  I  HO-C-H  AcO-C-H * H-C-OAr" H-i-OAc  HO-C-H I H-C-OH  +  H-C-OH H-A-OH  H-C-OH  AHOH 2  CH^OAc  CHpH  HO  CH^OH —O  —O  —Q HO CHOH  64  OH  .OH  OH  (117)  (122)  CHpH (117)  I  C HPH  (123)  (121)  (116)  HO W  H  CH-NO,  (124)  91 6lH^OH  -  (115)  113  under v a r i o u s c o n d i t i o n s , and e s t a b l i s h e d optimum  c o n d i t i o n s f o r i t s p r e p a r a t i o n i n a reasonably h i g h s t a t e of p u r i t y .  T h i s was  siderable y i e l d of  (.115)  (115)  confirmed by the f o r m a t i o n of a con-  of the  p-nitrophenylhydrazone  from the syrupy product.  thus prepared was  When the  derivative  anhydro-sugar  r e a c t e d w i t h nitromethane  i n the.  presence of sodium methoxide under anhydrous c o n d i t i o n s , a c c o r d i n g t o the g e n e r a l procedure of F i s c h e r and Sowden the immediate f o r m a t i o n of a copious amount of white was  observed, presumed to be the a n t i c i p a t e d  s a l t s of n i t r o a l c o h o l s  (125)  and  146  J  ,  solid  aci-sodium  F o l l o w i n g de-  (126).  i o n i s a t i o n by passage of an aqueous s o l u t i o n of the product through Dow ex 50(H-') r e s i n , a syrup was f r a r e d spectrum  obtained whose i n -  ( F i g u r e 4A) c l o s e l y resembled  4B) of the mixture  that ( F i g u r e  of 1 - d e o x y - l - n i t r o - D - m a n n i t o l and  (.119)  l - d e o x y - l - n i t r o - D - g l u c i t o l p r e v i o u s l y o b t a i n e d d u r i n g the p r e p a r a t i o n of 2-amino~2~deo:xy-D-mannose h y d r o c h l o r i d e ' (116)  (Equation 6 3 ) .  I n f r a r e d evidence, and the f a c t  that  t h i n l a y e r chromatography of the product showed i t to consist  e s s e n t i a l l y of two  t h a t the f i r s t  c l o s e l y - m o v i n g components, i n d i c a t e d s y n t h e s i s of 3,6-anhydro-  stage of the attempted  QH 0H —O 2  (pH  (115)  +  -C-CHNO I 2 2  OH H  0  •c-C -CHNQ Il  H  (125)  65  OH (126)  2  2  I n f r a r e d Spectra of: A and C - n i t r o a l c o h o l s and acetylated n i t r o a l c o h o l s from 2,5-anhydro-D-mannose B and D - n i t r o a l c o h o l s and acetylated n i t r o a l c o h o l s from D-arabinose  Figure 4  - ilii 2 - d e o x y - D - g l u c o - h e p t l t o l had gone as planned.  Acetylatlon  of t h e product with a c e t i c anhydride c o n t a i n i n g a t r a c e o f s u l p h u r i c a c i d gave a mixture o f a c e t a t e s whose i n f r a r e d spectrum (Figure 4C) a l s o c l o s e l y resembled t h a t o f the mixture (120) p r e v i o u s l y obtained (119) N0  ( F i g u r e 4D),  by t h e a c e t y l a t l o n o f  showing a b s o r p t i o n  c h a r a c t e r i s t i c of  s t r e t c h i n g v i b r a t i o n s at 155© and 1365 cm" . 1  g  When  the a c e t y l a t e d m a t e r i a l was r e f l u x e d i n benzene s o l u t i o n w i t h sodium hydrogen carbonate, the i n f r a r e d spectrum o f the product which was i s o l a t e d was v i r t u a l l y unchanged from that o f the a c e t y l a t e d r e a c t a n t .  E l i m i n a t i o n of  a c e t i c a c i d , t o g i v e the r e q u i r e d n i t r o - o l e f i n , on ; ... treatment with m i l d base would presumably have been c l e a r l y apparent by a s h i f t t o lower f r e q u e n c i e s and  o f the asymmetric  symmetric s t r e t c h i n g v i b r a t i o n s o f the NOg gjpoup on  154 conjugation  , as was evidenced by the two bands at 1510  -1 cm  -1 and 1350 cm  i n the i n f r a r e d spectrum o f D-arabino-  tetraacetoxy-l-nitro-l-hexene  (121).  Prolonged r e f l u x i n g  i n benzene s o l u t i o n with sodium hydrogen carbonate, and s i m i l a r treatment with t h e s t r o n g e r base sodium a c e t a t e , f a i l e d t o b r i n g about the r e q u i r e d e l i m i n a t i o n .  T h i s approach  to the s y n t h e s i s o f a 3 , 6 - a n h y d r o - 2 - d e o x y - h e p t i t o l , which apparently  showed some promise i n the e a r l i e r stages, was  t h e r e f o r e abandoned as an a l t e r n a t i v e s t r u c t u r a l proof, des c r i b e d below, became a v a i l a b l e .  - 115 (d)  C o r r e l a t i o n w i t h 2,6-Anhydro-3-deoxy-D-gluco-heptltol  (130)  I t was subsequently p o s s i b l e t o e s t a b l i s h the s t e r e o chemistry o f one of the enantiomeric t e t r o l ethers p r e v i o u s l y d e s c r i b e d , and hence the a b s o l u t e c o n f i g u r a t i o n s o f both F r a c t i o n s A and B,/by c o r r e l a t i o n w i t h the t e t r o l ether d e r i v e d from a 2 , 6 - a n h y d r o - 3 - d e o x y - h e p t i t o l  (108) o f known  155 stereochemistry.  Rosenthal and Koch  have i n v e s t i g a t e d  the oxo r e a c t i o n o f the c o m m e r c i a l l y - a v a i l a b l e 3 , 4 , 6 - t r i O - a c e t y l - D - g l u c a l (20 a ) .  The products from t h i s  were found t o be completely analogous  reaction  t o those obtained  from the r e a c t i o n s o f 3 , 4 , 6 - t r i - O - a c e t y l - D - g a l a c t a l ( 4 0 ) and 3 , 4 - d i - O - a c e t y l - J D - x y l a l ( 2 2 ) . mixture of i s o m e r i c heptitols  (127)  When the c a t a l y s t - f r e e  4,5,7-tri-0-acetyl-2,6-anhydro-3-deoxy-  and (128) r e s u l t i n g from the oxo r e a c t i o n  of (20 a) was r e a c t e d w i t h p-bromobenzenesulphonyl  bromide  i n p y r i d i n e , one o f the isomers, ( 1 2 7 ) , was r e a d i l y as the c r y s t a l l i n e O-p-bromobenzenesulphonate,  isolated  X-ray  156 a n a l y s i s of the c r y s t a l l i n e d e r i v a t i v e  e s t a b l i s h e d that  i t was the 1-0-p-bromobenzenesulphonyl d e r i v a t i v e  (129) °f  4 , 5 , 7 - t r i - 0 - a c ety1-2,6-a nhydro-3-deoxy-D-gluco-heptitol (127).  D e a c e t y l a t i o n of the c a t a l y s t - f r e e oxo product and  f r a c t i o n a t i o n by paper chromatography gave two i s o m e r i c anhydrodeoxyheptitols.  One o f t h e s e , 2,6-anhydro-3-deoxy-  D - g l u c o - h e p t i t o l (13©) was a l s o o b t a i n e d from the 1-0-pbromobenzenesulphonyl  derivative  ( 1 2 9 ) , o f known c o n f i g u r a t i o n ,  - Il6 "by standard  procedures  CH,OAc  CH OAc z  ^OAc  —OvCh^OH. AcO  OAc  AcO  +  A,0  (20a)  OAc Ch^OH (128)  ci-yoAc —O^HpBs AcO  OAc (130)  (129)  2,6-Anhdyro-3-deoxy-D-gluco-hept11o1 (130)  was  s u b j e c t e d t o p e r i o d a t e o x i d a t i o n and the r e s u l t i n g d i a l d e hyde was  reduced with sodium borohydride,  u s i n g the  pro-  cedure d e s c r i b e d p r e v i o u s l y , to a f f o r d 2 - d e o x y - 3 - 0 - ( 1 , 3 dihydroxy-2-propyl)-L-glycero-tetritol dextrorotatory,  (  [p^j) + 2 6 ° ) , as was  (95).  This  the t e t r o l  was  ether  ;H OH 2  HC—O-  A HPH  (95) (130)  Fraction A  6'  from F r a c t i o n AJ v a t i v e , m.p.  (95)  formed a t e t r a - O - p - n i t r o b e n z o y l  1 5 1 - 1 5 2 , whose m e l t i n g p o i n t was  not  c  on admixture with the corresponding ether from F r a c t i o n A, and  the two  same s p e c i f i c r o t a t i o n s and  p-nitrobenzoates  infrared spectra.  the B-gluco-isomer ( 1 3 0 ) , t h i s being the o n l y  age  (95)  s u r v i v i n g i n the t e t r o l ether  of the C-4  - C-5  bond and  reduction.  tetrol  had  the  Therefore as  had  asymmetric  formed by  s a f e l y assumed t h a t the secondary h y d r o x y l and C-5  depressed  d e r i v a t i v e of the  F r a c t i o n A must have the B - c o n f i g u r a t i o n at C - 2 ,  centre  deri-  cleav-  As i t c o u l d  be  groups at  C-4  of the anhydrodeoxyheptitols were unchanged i n  c o n f i g u r a t i o n from those of B - g a l a c t a l , the s t r u c t u r e of F r a c t i o n A was  t h e r e f o r e e s t a b l i s h e d as 2,6-anhydro-3-deoxy-  B-galacto-hept11o1 (91).  As F r a c t i o n B d i f f e r e d from  F r a c t i o n A only i n c o n f i g u r a t i o n at C - 2 , anhydro-3-deoxy-B-talo-heptitol (v)  t h i s must be  2,6-  (90).  S t e r i c Aspects of Hydroxymethylation The  r e a c t i o n s of a c e t y l a t e d g l y c a l s with  carbon  monoxide and hydrogen to g i v e , as major products, approximately equal r a t i o of the two  an  p o s s i b l e products r e -  s u l t i n g from a d d i t i o n of a hydroxymethyl group at G - l of the g l y c a l would appear to be g e n e r a l ; t h i s i s supported by the f a c t that e s s e n t i a l l y s i m i l a r r e s u l t s are by the oxo  r e a c t i o n of 3 , 4 , 6 - t r i - O - a c e t y l - B - g l u c a l  and 3,4-di-O - a c e t y l - B - a r a b i n a l  (32)  1 2 2  .  obtained (20  a) -^ 1  That hydroxymethylation  - 118  -  occurs at the carbon of the double bond (X to the r i n g oxygen of the g l y c a l s Is c o n s i s t e n t w i t h the f i n d i n g s of workers r e g a r d i n g  the a p p l i c a t i o n of the oxo  other  r e a c t i o n to 25  c y c l i c v i n y l ethers  such as 2 , 3 - d i h y d r o - 4 H - p y r a n ( l )  . . 26 and  furan  (9)'  .  However, i n view of the s t r o n g  dependence of the oxo general,  and  steric  r e a c t i o n when a p p l i e d to o l e f i n s i n  the apparent s t e r i c f a c t o r s i n v o l v e d i n a d d i -  t i o n r e a c t i o n s of g l y c a l s , both of which were d i s c u s s e d the General I n t r o d u c t i o n ,  i t i s s u r p r i s i n g that  mately equal amounts of two always o b t a i n e d ,  in  approxi-  s t r a i g h t - c h a i n products  are  as a r e s u l t of c i s a d d i t i o n t o both s i d e s  of the g l y c a l double bond, r a t h e r than a preponderance of the isomer which would r e s u l t from a d d i t i o n at the l e a s t hindered  side. 17  Heck and Breslow  found t h a t , at oxo  temperatures, the formation from o l e f i n and  of a l k y l c o b a l t t e t r a c a r b o n y l s  cobalt hydrotetracarbonyl  i n what i s assumed to be the f i r s t is rapidly reversible. d i s t r i b u t i o n obtained hydrotetracarbonyl  7-9),  (Equations  stage o f ' t h e oxo  These workers found t h a t the  reaction, product  by r e a c t i o n of o l e f i n s w i t h c o b a l t  at low  temperature was  as that, found under normal oxo whereas i s o v a l e r a l d e h y d e r e a c t i o n of i s o b u t y l e n e trimethylacetaldehyde,  reaction  conditions:  o f t e n not  the same  f o r example,  i s the major product from the (equation  15),  at low  oxo  temperature  r e s u l t i n g from a d d i t i o n to the more  - 119  -  h i g h l y s u b s t i t u t e d s i d e of the double bond, predominates. These f i n d i n g s were e x p l a i n e d initial  by the f a c t t h a t , as  the  a d d i t i o n to the double bond i s r e v e r s i b l e , the  product d i s t r i b u t i o n at h i g h temperature i s a r e f l e c t i o n of the r e l a t i v e s t a b i l i t i e s their i n i t i a l  of the adducts, r a t h e r  concentrations,  than  the t e r m i n a l aldehyde being  more s t a b l e yet forming l e s s r e a d i l y . A s i m i l a r explanation  c o u l d account f o r the  isomer d i s t r i b u t i o n from the oxo  r e a c t i o n of g l y c a l s .  Assuming that a d d i t i o n to the l e a s t - h i n d e r e d double bond i s favoured, and  observed  that the f i r s t  s i d e of  the  stage of  the  r e a c t i o n leads to g l y c o s y l c o b a l t t e t r a c a r b o n y l s  .according  to the g e n e r a l l y accepted mechanism, i t would be  reasonable  to suppose that the adduct so formed (e.g. di-O-acetyl-D-xylal)  would be  (131)  from  l e s s s t a b l e than the  t i v e , k i n e t i c a l l y less-favoured  adduct  (132)  with  3,4-  alternathe  -Co(CO)^ group i n e q u a t o r i a l o r i e n t a tlonj|and would r e v e r t more r e a d i l y to the g l y c a l .  AcO•Co(£0)  4  (131)  (132)  - 120 C.  -  H y d r o f o r m y l a t l o n of 3 , 4 - D i - O - a c e t y l - D - x y l a l  In s e c t i o n A i t was  shown t h a t the r e a c t i o n of  3,4-  d i - O - a c e t y l - D - x y l a l w i t h 3 moles of s y n t h e s i s gas gave a mixture c o n s i t i n g predominantly of the 2 , 3 - d l - 0 - a c e t y l - l , 5 anhydro-4-deoxy-hexltols and  (45)  (74)  and  (75),  from which  were obtained on d e a c e t y l a t i o n .  assumption  (44)  An a_ p r i o r i  r e g a r d i n g the oxo r e a c t i o n of g l y c a l s i s that  the i n i t i a l products are aldehydes, r e s u l t i n g from the h y d r o f o r m y l a t l o n of the double bond, and t h a t these subsequently undergo hydrogenation t o a f f o r d the observed products.  On t h i s b a s i s i t was  reasonable to assume that  t e r m i n a t i o n of the r e a c t i o n at the p o i n t where o n l y 2 moles of s y n t h e s i s gas had r e a c t e d would g i v e a product  consisting  predominantly of aldehydes; f o r example the a n t i c i p a t e d products from the h y d r o f o r m y l a t l o n of 3 , 4 - d i - O - a c e t y l - D xylal  (22)  would be the i s o m e r i c 4 , 5 - d i - 0 - a c e t y l - 2 , 6 -  anhydro-3-deoxy-aldehydo-hexoses (133)  and  (134).  - 121 A c e r t a i n amount of evidence has been obtained p r e v i o u s l y t o show that aldehydlrj compounds are present i n products o b t a i n e d by the oxo r e a c t i o n of g l y c a l s ; f o r example, t h i s has been i n d i c a t e d by the r e d u c i n g power o f r e a c t i o n products From the r e a c t i o n of 3*4,6-tri-  to Somogyi's r e a g e n t - ^ . 1  x ' 64 0-acety1-D-gluca1 (20 a) w i t h carbon monoxide and hydrogen , a s i n g l e c r y s t a l l i n e component was I s o l a t e d , i n a d d i t i o n to the a c e t y l a t e d a l c o h o l s  (127)  and  (128),  which was though  to be an O-acetylated-anhydrodeoxy-aldehydo-heptose, (130)  on d e a c e t y l a t i o n and r e d u c t i o n .  giving  A d d i t i o n a l evidence  f o r the presence of an aldehydo-compound i n the hydroformyl a t i o n product o f (20 a) has been o b t a i n e d ^ n i t s r e a c 1  0  t i o n w i t h e t h y l mercaptan, as a homogeneous syrup was i s o l a t e d by chromatography whose n.m.r. spectrum was s i s t e n t w i t h an a c e t y l a t e d (i)  con-  thioacetal.  Reaction. C o n d i t i o n s and.Product  Isolation  C o n d i t i o n s f o r the r e a c t i o n of 3,4-di-O-acetyl-Dx y l a l with  2  E q u a t i o n 68)  moles of s y n t h e s i s gas  >(133) + (134),  were s i m i l a r t o those p r e v i o u s l y d e s c r i b e d  f o r i t s hydroxymethylation temperature  ((22)  (115°) was  ( S e c t i o n A ) , except t h a t a lower  employed f o r the r e a c t i o n , to favour  the f o r m a t i o n of aldehydes.  Once a b s o r p t i o n of s y n t h e s i s  gas commences, as evidenced by a decrease i n the p r e s s u r e i n d i c a t e d on the guage a t t a c h e d t o the r e a c t i o n v e s s e l , i t r a p i d l y overshoots the h y d r o f o r m y l a t i o n stagehand  i t was  - 122 necessary tical to  -  t o c a r r y out a p r e l i m i n a r y experiment under Iden-  c o n d i t i o n s i n order to determine the p o i n t e q u i v a l e n t  the a b s o r p t i o n of 2 moles of gas, when the r e a c t i o n was  quenched by immersion of the r e a c t i o n v e s s e l In i c e . The  r e a c t i o n product  was  isolated in a similar  manner to that d e s c r i b e d p r e v i o u s l y . moved from the r e a c t i o n mixture column w i t h petroleum  ether.  e l u t e d w i t h benzene-isopropyl (from 12.0  C a t a l y s t was  re-  by e l u t i o n from a  The  Florisil  f r a c t i o n which was  then  a l c o h o l weighed only 10.0  g of (22)) a f t e r e v a p o r a t i o n of s o l v e n t  g  and  t h e r e f o r e d i d not represent the whole of the r e a c t i o n produet.  A f u r t h e r 2.5  the petroleum and was  g of a mobile syrup was  i s o l a t e d from  e t h e r e l u a t e ; t h i s c r y s t a l l i s e d on  standing,  i d e n t i f i e d as 3 , 4 - d i - O - a c e t y l - D - x y l a l by  son of i t s t h i n l a y e r chroraatogram and  infrared  a g a i n s t an a u t h e n t i c specimen of the g l y c a l .  comparispectrum  I t was  ap-  parent, on t h i n l a y e r chromatography of the main f r a c t i o n e l u t e d from F l o r i s i l w i t h b e n z e n e - i s o p r o p y l it  a l c o h o l , that  a l s o contained an a p p r e c i a b l e q u a n t i t y of the  unreacted  g l y c a l , t h i s being f u r t h e r i n d i c a t e d by a sharp peak at 1640  cm  1  i n the i n f r a r e d spectrum of t h i s f r a c t i o n .  In  a d d i t i o n to 3 , 4 - d i - O - a c e t y l - D - x y l a l , t h i n l a y e r chromatography r e v e a l e d the presence of a compact mixture components, ( c l o s e l y resembling appearance the mixture  i n m o b i l i t y and  r e s u l t i n g from the  of other  general  hydroxymethylation  of  (22)  (Section A)).  T h i s mixture of r e a c t i o n products,  being w e l l separated from the faster-moving g l y c a l , r e a d i l y i s o l a t e d by chromatography onj a column of  was  alumina. 3>4-  A p o r t i o n of the main f r a c t i o n thus separated gave  d i - 0 _ - a c e t y l - D - x y l a l and r e a c t i o n products i n the r a t i o of  2:3.  Taking i n t o account the a d d i t i o n a l amount of  g l y c a l e l u t e d from P l o r i s i l along w i t h the c a t a l y s t , the composition of the mixture obtained from the r e a c t i o n t h e r e f o r e approximately 50$ unreacted  was  3*4-di-0-acetyl-D-  x y l a l and an equal amount of s a t u r a t e d p r o d u c t s . Comparison of the r e a c t i o n product, separated  from  unreacted g l y c a l as d e s c r i b e d above, w i t h the product v i o u s l y obtained by the r e a c t i o n of (22) s y n t h e s i s gas  pre-  w i t h 3 moles of  ( S e c t i o n A), showed that the two were p r a c t i -  c a l l y i n d i s t i n g u i s h a b l e on the b a s i s of t h i n l a y e r chromatograms and I n f r a r e d s p e c t r a .  However a d i f f e r e n c e  was  found i n the low f i e l d r e g i o n of the n.m.r. s p e c t r a , as only the product i s o l a t e d from the above r e a c t i o n showed a single, peak at  & = 9 . 3 5 ppm,  c h a r a c t e r i s t i c of a l d e h y d i c  IRQ  protons  .  On the assumption  that t h i s was  due to the  presence of compounds ((133) + ( 1 3 4 ) ) , and t h a t the of  the mixture comprised  t h e i r r e d u c t i o n products  remainder ((74)  +  (75))> the i n t e n s i t y of the low f i e l d a b s o r p t i o n r e l a t i v e to  the combined i n t e n s i t i e s of the acetoxy-hydrogen  i n the r e g i o n of  S  - 2.0  - 2.2  ppm  signals  indicated that approxi-  mately 20$ of aldehydo-compounds were present i n the  mixture  - 12.4  -  R e s u l t s of t h i n l a y e r chromatography c l e a r l y  precluded  the p o s s i b i l i t y of e f f e c t i n g a s e p a r a t i o n of the by chromatographic (ii)  mixture  procedures.  Reac tlo.n^.-lth;^ 2i4^B-ihitrophenyl.hydra z i n e C o n f i r m a t i o n of the presence  of aldehydie  components  i n the main f r a c t i o n from the attempted  hydroformylatlon  r e a c t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l was  sought by r e a c t i n g  a p o r t i o n of the product w i t h a t e s t s o l u t i o n of 2 , 4 - d i n i t r o ii • 160 phenylhydrazine, which was prepar/e|3, i n the u s u a l way ,  \  by d i s s o l v i n g the reagent l u t i n g with ethanol. s o l i d was  i n aqueous s u l p h u r i c a c i d and d i -  Immediate p r e c i p i t a t i o n of a yellow  indeed observed;  on s t a n d i n g .  t h i s changed to an orange o i l  However, a c o n t r o l experiment i n which pure  3 , 4 - d i - O - a c e t y l - D - x y l a l , known to be present i n the hydro-, f o r m y l a t i o n product, was way  s e p a r a t e l y t r e a t e d i n the same  a l s o r e s u l t e d i n the p r e c i p i t a t i o n of an or&nge s o l i d  i n c o n s i d e r a b l e amount.  C l e a r l y , under these c o n d i t i o n s ,  i s o l a t i o n of any d e r i v a t i v e s r e s u l t i n g from the r e a c t i o n w i t h 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e of aldehydo-hexoses present i n the mixture would have been corapiicated^^y;;'fehe;--presence of d e r i v a t i v e s o r i g i n a t i n g from the g l y c a l . of the l a t t e r product was  The  nature  not i n v e s t i g a t e d f u r t h e r , but i s  presumed to r e s u l t from one  or both of two known r e a c t i o n s  of g l y c a l s under aqueous a c i d c o n d i t i o n s , namely the a d d i t i o n  of water a c r o s s the double  bond l e a d i n g t o 2-deoxy-aldoses  ,  l6l and t h e i r ready  isoraerisation to pseudo-glycals  .  Addi-  t i o n a l c o m p l i c a t i o n s such as d e a c e t y l a t i o n would be a n t i c i pated under these s t r o n g l y a c i d c o n d i t i o n s , i n d i c a t e d by the observed  change from a s o l i d to an o i l .  C o n d i t i o n s were t h e r e f o r e e s t a b l i s h e d f o r r e a c t i n g the h y d r o f o r m y l a t i o n product with i n the absence of s t r o n g a c i d .  2,4-dinitrophenylhydrazine  A s o l u t i o n o f the reagent  i n e t h a n o l , s a t u r a t e d at the b o i l i n g p o i n t , was added i n p o r t i o n s t o a s o l u t i o n of the r e a c t i o n product  i n ethanol  c o n t a i n i n g a t r a c e o f a c e t i c a c i d , a l s o heated  t o the b o i l i n g  p o i n t on a steam bath.  R e a c t i o n was i n d i c a t e d by the f a c t  that a f t e r each a d d i t i o n the orange c o l o u r faded t o y e l l o w ; when the c o l o u r no l o n g e r faded a f t e r h e a t i n g f o r s e v e r a l minutes, i n d i c a t i n g t h a t a s l i g h t  excess  of the h y d r a z i n e  was p r e s e n t , water was added t o t u r b i d i t y . a pale yellow s o l i d separated,•which by f i l t r a t i o n .  On s t a n d i n g ,  was r e a d i l y I s o l a t e d  Under the same c o n d i t i o n s 3 , 4 - d i - O - a c e t y l -  D - x y l a l d i d not r e a c t , and only unchanged 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e was i s o l a t e d f o l l o w i n g d i l u t i o n o f the mixture w i t h water. T h i n l a y e r chromatography of the y e l l o w s o l i d from t h i s r e a c t i o n r e v e a l e d the presence ponents, t o g e t h e r w i t h t r a c e s of o t h e r s .  obtained  of two major comThe two major pro-  ducts of the r e a c t i o n , the f a s t e r moving o f which w i l l be  - 126  -  designated F r a c t i o n X and the slower, F r a c t i o n Y, moved very c l o s e l y t o g e t h e r on s i l i c a g e l u s i n g a v a r i e t y of developing s o l v e n t s . i n the mixture was  The absence of c o l o u r l e s s  demonstrated  impurities  on s p r a y i n g t h i n  layer  chromatograms w i t h a s u l p h u r i c - n i t r i c a c i d reagent heating.  From an amount of 1.2  from the oxo r e a c t i o n , 0.4  g of the main f r a c t i o n  g of 2 , 4 - d i n i t r o p h e n y l h y d r a z o n e s ,  c o n s i s t i n g e s s e n t i a l l y of F r a c t i o n s X and Y, was On the assumption  and  isolated.  t h a t X and Y were d e r i v a t i v e s of i s o m e r i c  d i - Q - a c e t y l - a nhydrpdeoxy-a ldehydo-hexoses  (133)  and  (134),  i  and t h a t d e r i v a t i s a t i o n was weight  of hydrazones  roughly q u a n t i t a t i v e , the  i s o l a t e d t h e r e f o r e i n d i c a t e d the  presence of approximately 15$ The n.m.r. spectrum  of aldehydes  i n the mixture.  of the product obtained by  reaction  w i t h 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e confirmed i t s composition . as a mixture of two  2,4-dinitrophenylhydrazones  of a c e t y -  l6l l a t e d anhydrodeoxy-aldehydo-hexoses. low f i e l d s i g n a l s due to -NH  The r e a d i l y - a s s i g n a b l e  and protons of the d i n i t r o p h e n y l  group showed i d e n t i c a l chemical s h i f t s f o r both isomers cept f o r the aromatic C-6 ting  (J = 9-10  proton, which has a l a r g e  c/s) by c o u p l i n g w i t h the  A p a i r of o v e r l a p p i n g doublets ( J = and 7«95 ppm  demonstrated  split-  ortho-hydrogen.  9 c/s) at $ =  the presence of a mixture  7.87 of  isomers, t h i s a l s o being shown by 3 a c e t a t e s i g n a l s at high f i e l d .  The doublet at  a s s i g n a b l e to the  S =7.85 ppm  (J =6  c/s)  ex-  was  -N=C-H group and confirmed t h a t the  -  127/-  d e r i v a t i v e s were of aldehydes ()  161  r a t h e r than ketones/.  S e p a r a t i o n of F r a c t i o n s X and Y  a  When the mixture of 2,4-dinitrophenylhydrazones heated w i t h a s m a l l volume of e t h a n o l , p a r t i a l  solution  of the mixture o c c u r r e d , l e a v i n g a g r a n u l a r y e l l o w which was  not r e a d i l y s o l u b l e i n e t h a n o l .  was  solid  Upon i s o l a t i o n  and examination by t h i n l a y e r chromatography, the i n s o l u b l e p o r t i o n showed only one zone corresponding t o the moving of the two mixture.  components ( F r a c t i o n Y) present i n the  The m a t e r i a l thus i s o l a t e d c r y s t a l l i s e d  from chloroform-hexane 226°,  [<?<Gn - 6 0 ° ,  slower-  readily 225-  as f i n e yellow needles, m.p.  and gave an elemental a n a l y s i s i n agree-  ment w i t h t h a t r e q u i r e d f o r a 2,4-dinitrophenylhydrazone of a  4,5-di-0-acetyl-2,6-anhydro-3-deoxy-aldehydo-hexose  ((133) or (134)).  The n.m.r. spectrum  of t h i s  d i f f e r e d c h i e f l y from that of the mixture a c e t a t e peaks of equal i n t e n s i t y a doublet C-6  ( J = 9 c/s) at £ = 7 . 8 5  i n showing  ( § =2.13 ppm,  fraction  and 2.17  two ppm);  a s s i g n a b l e t o the  proton of the 2 , 4 - d i n i t r o p h e n y l group, confirmed the  homogeneity of the product.  Thus, f r a c t i o n a l s o l u t i o n of  the mixture a f f o r d e d a convenient procedure  f o r the separa-  t i o n of F r a c t i o n Y from F r a c t i o n X i n a p p r e c i a b l e amounts, thereby f a c i l i t a t i n g i t s f u r t h e r examination. of a l a r g e r q u a n t i t y ( 6 . 8  Treatment  g) of the main f r a c t i o n  (from  - 128 the r e a c t i o n of (22)  w i t h 2 moles of s y n t h e s i s gas) w i t h  2 , 4 - d i n i t r o p h e n y l h y d r a z o n e as d e s c r i b e d  p r e v i o u s l y gave  2.4  g of the mixed hydrazones, from which 0 . 9 g of pure F r a c t i o n Y was  obtained  ethanol,  by t r i t u r a t i o n of the mixture w i t h warm  and r e c r y s t a l l i z a t i o n of the i n s o l u b l e p o r t i o n .  I s o l a t i o n of the other d e r i v a t i v e , F r a c t i o n X, from the a l c o h o l - s o l u b l e r e s i d u e , which contained X and Y, presented a d i f f i c u l t lar  both F r a c t i o n s  problem because of the s i m i -  m o b i l i t i e s of the two f r a c t i o n s on chromatography.  I t was  p o s s i b l e to i s o l a t e a s m a l l amount o f the f a s t e r -  moving component, X, s u f f i c i e n t f o r c h a r a c t e r i s a t i o n , by chromatography on t h i c k p l a t e s of s i l i c a  g e l u s i n g the  technique of m u l t i p l e development, with c h l o r o f o r m  as de-  veloping  solvent.  way  had m.p.  132°,  for  C-^gH-^gN^O^.  The d e r i v a t i v e i s o l a t e d i n t h i s -16°,  and a l s o analysed  A q u a n t i t a t i v e determination  of the two i s o m e r i c  showed that X and Y were present  (b)  of the amounts  2 , 4 - d i n i t r o p h e n y l h y d r a z o n e s i n the mix-  t u r e , by chromatography on s i l i c a  of  satisfactorily  g e l i n the same way, i n the approximate r a t i o  1:2. I d e n t i f i c a t i o n of F r a p t i o n Y An adequate amount of F r a c t i o n Y b e i n g . a v a i l a b l e ,  i t was  p o s s i b l e to convert  this  2,4-dinitrophenylhydrazone  to the f r e e aldehydo-hexose, which was then i d e n t i f i e d by d e a c e t y l a t i o n and r e d u c t i o n deoxyhexitol  to the corresponding anhydro-  of known s t r u c t u r e .  Conversion of F r a c t i o n Y  r  to  "  129'  the f r e e aldehyde was e f f e c t e d by e q u i l i b r a t i o n o f the  hydrazone w i t h an excess of p y r u v i c a c i d , f o l l o w i n g a proced-  162 a p p l i e d 'by Mattox and K e n d a l l the  to the h y d r o l y s i s o f  2 , 4 - d i n l t r o p h e n y l h y d r a z o n e of a s t e r o i d a l ketone.  The  2 , 4 - d i n i t r o p h e n y l h y d r a z o n e of p y r u v i c a c i d so formed was r e a d i l y removed from the r e a c t i o n mixture by f i l t r a t i o n , and by e x t r a c t i o n w i t h sodium hydrogen carbonate s o l u t i o n . A syrupy product was i s o l a t e d from t h i s r e a c t i o n which was not completely c h a r a c t e r i s e d J however, the f a c t that i t 159 was an aldehydo-compound a sharp s i g n a l at  was shown by the presence o f  S=9*35  ppm i n i t s n.m.r. spectrum,  measured i n d e u t e r i o c h l o r o f o r m s o l u t i o n .  I t i s thought  that the product probably e x i s t e d as a mixture o f f r e e and hydrated aldehyde, as the i n t e n s i t y o f t h i s low f i e l d  signal  r e l a t i v e t o the remainder o f the spectrum was only about that required f o r a aldehydo-hexose  half  4,5-di-0^abetyl-2,6-anhydro-3-deoxy-  ((133)  or ( 1 3 4 ) ) .  A d d i t i o n a l evidence f o r  t h i s was t h e presence i n the i n f r a r e d spectrum o f bands a s s i g n a b l e to both aldehyde  (C=0 s t r e t c h i n g at 1700 cm"  1  i n a d d i t i o n t o a c e t a t e a b s o r p t i o n at 1740 cm"*'") and h y d r o x y l groups.  That the l a t t e r were not a r e s u l t o f d e a c e t y l a t i o n  d u r i n g and subsequent t o the exchange r e a c t i o n w i t h p y r u v i c a c i d was shown by the f a c t t h a t when a p o r t i o n o f the syrupy product was r e a c t e d w i t h 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e , the o r i g i n a l c r y s t a l l i n e d e r i v a t i v e , F r a c t i o n Y, was o b t a i n e d .  Wolfrom  163,164 have observed the ready.formation, by 0 -  and co-workers  a c e t y l - a l d e h y d o - s u g a r s , of c r y s t a l l i n e hydrates and a l c o h o l a t e s which have been shown t o be a l d e h y d r o l (135) (136)  derivatives;  t h e i r f o r m a t i o n accounts f o r the mutaro-  M  H  HO-C-OH  and h e m i a c e t a l  <  H  Q  Y  H  M  yO R  Q  H  >RO-C-OH  (135)  6  9  (136)  t a t i o n of aldehydo-sugars i n aqueous and a l c o h o l i c The a l d e h y d i c product -thus i s o l a t e d was  solutions.  readily  i d e n t i f i e d as  4,5-di-0-acetyl-2,6-anhydro-3-deoxy-aldehydo-  D-lyxo-hexose  (133)•  A p o r t i o n was r e a c t e d w i t h sodium  borohydride i n aqueous methanol, whereby the aldehyde was  group  reduced t o hydroxymethyl,. and simultaneous h y d r o l y s i s  of the a c e t y l groups was  e f f e c t e d i n the b a s i c medium.  product I s o l a t e d from t h i s r e a c t i o n was  The  s u b j e c t e d t o chroma-  tography on paper a l o n g s i d e c o n t r o l spots of the anhydrodeoxyhexitols  (44)  and  ( 4 5 ) , . ( S e c t i o n A), and thereby i d e n -  t i f i e d w i t h the faster-moving isomer, 2,6-anhydro-3-deoxy-Darabino-hexitol  (44) .  The a l d e h y d i c p r e c u r s o r there^qre: had  the D - l y x o - c o n f i g u r a t i o n  (.133), and F r a c t i o n Y was  acetyl-2,6-anhydro-3-deoxy-aldehydo-D-lyxo-hexose phenylhydrazone.  4,5-di-O2,4-dinitro-  I t f o l l o w e d that F r a c t i o n X must be the  c o r r e s p o n d i n g d e r i v a t i v e of  4,5-di-0-acetyl-2,6-anhydro-3-deoxy  a 1dehydo-D-xy1o-hexose ( 1 3 4 ) , as the other major component  - 131 (45),  p r e v i o u s l y I s o l a t e d from the hydroxymethylation of  3,4-di-O-acetyl-D^xylal,  had  the L - x y l o - c o n f i g u r a t i o n .  Thus  CHPH  Fraction  y'i  (  Y  70  IHO-C-H 9  H-C-OH  D-arabino-(44)  D-iyxo-.(l33)  HO-^-HH Fraction  .H-C-OH  X  71  HPH D-xylo-  (134)  L-xylo-  (45)  I t i s of i n t e r e s t t h a t , whereas the anhydrodeoxyhexitols  (44)  methylation  (45),  and  p r e v i o u s l y i s o l a t e d from the hydroxy-  of 3 , 4 - d i - O - ^ c e t y l - D - x y . l a l  n e a r l y equal p r o p o r t i o n s , (133)  were present  the amount of the  D-lyxo-hexose  i s o l a t e d (as F r a c t i o n Y) from the i n t e r m e d i a t e  of the r e a c t i o n was  considerably  of i t s isomer ( 1 3 4 ) . hydroformylatlon  I t has  1  stage  g r e a t e r than the amount  been shown that the r a t e of  of o l e f i n s depends on the  of the double bond ^, and  in  accessibility  i t i s reasonable to suppose that  a s i m i l a r e f f e c t w i l l operate i n the hydrogenation  stage,  which i s a l s o considered  to proceed v i a an  intermediate  20 Tt-complex with c o b a l t h y d r o t r i c a r b o n y l t h e r e f o r e , that the c a r b o n y l group of  ..  I t i s suggested  (13*0, being i n equa-  t o r i a l o r i e n t a t i o n to the r i n g , i s more a c c e s s i b l e f o r complex formation,  and  (134)  i s more r a p i d l y removed from the  r e a c t i o n mixture by hydrogenation that i s (133)> In which the formyl group i s presumably a x i a l .  i  .  1  (45)  (iii)  (44)  Aldehydo-hexoses by O x i d a t i o n The  attempted h y d r o f o r m y l a t i o n  above c l e a r l y showed that the oxo D - x y l a l was (133)  and  of H e x i t o l s experiments  r e a c t i o n of  described  3,4-di-0-acetyl-  not a s a t i s f a c t o r y source of aldehydo-hexoses ( 1 3 4 ) , as these were a p p a r e n t l y  to a l c o h o l s and  too r e a d i l y reduced  d i d not accumulate i n the r e a c t i o n mixture.  Some experiments were t h e r e f o r e c a r r i e d out with a view to preparing  (133)  and  (134)  by o x i d a t i o n of the more a c c e s s i b l e ii -  mixture of dl-O-acetyl-anhydrodeoxyhiexitols (74) and (75), v r e s u l t i n g from the hydroxymethylation of (22) as d e s c r i b e d  133 In S e c t i o n A.  Few  -  methods are a v a i l a b l e f o r the o x i d a t i o n  of a l c o h o l s which stop short at the aldehyde  stage?  two  r e c e n t l y d e s c r i b e d , and somewhat s i m i l a r procedures were i n v e s t i g a t e d are those of Kornblum and and of P f i t z e r and M o f f a t t  1 6 6  which  co-workers  .  165 Kornblum and co-workers of aldehydes  have o b t a i n e d good y i e l d s  by the o x i d a t i o n of a v a r i e t y of b e n z y l i c and  s t r a i g h t c h a i n a l i p h a t i c t o s y l a t e s , on h e a t i n g w i t h a mixt u r e of sodium hydrogen carbonate The  and  dimethylsulphoxide.  l i m i t a t i o n s of the o x i d a t i o n , which I n i t i a l l y i n v o l v e s  displacement  of the t o s y l o x y group by  w i t h f o r m a t i o n of an Intermediate salt  dimethylsulphoxide,  dimethylsulphoxonium  were shown by the n o n - r e a c t i o n of neopentyl  An attempt  tosylate  to o x i d i s e the t e r m i n a l t o s y l o x y group of a  carbohydrate, l , 2 - 0 _ - i s o p r o p y l i d e n e - 6 - G - p - t o l y s u l p h o n y l - D g l u c o s e , d i d not g i v e the a n t i c i p a t e d aldehydobut the 5>6-carbonate  168  anhydro-4-deoxy-hexitols  compound  :  The mixture (74)  and  h y d r o f o r m y l a t i o n product from  (75)  (22)  of d i - 0 - a c e t y l - l , 5 comprising  ( S e c t i o n A) was  the tosylated  w i t h p - t o l u e n e s u l p h o n y l c h l o r i d e i n p y r i d i n e to g i v e the p r e v i o u s l y d e s c r i b e d crude mixture of i s o m e r i c 6-G-ptolylsulphonyl derivatives T h i s was  (76)  and  (77)  (equation  then r e a c t e d f o r 5 minutes at 1 5 0 ° ,  phere of n i t r o g e n , w i t h a mixture  52).  i n an atmos-  of sodium hydrogen c a r -  bonate and d i m e t h y l s u l p h o x i d e , a c c o r d i n g to the  procedure  of Kornblum and co-workers. c o l o u r e d syrup was  Prom t h i s r e a c t i o n a dark  i s o l a t e d whose i n f r a r e d spectrum  v i r t u a l l y unchanged from that of the mixture tolylsulphonyl derivatives  (76)  and  was  of 6-0-p-  (77).  R e s u l t s of a more p o s i t i v e nature were obtained by  166 the procedure  of P f i t z e r and M o f f a t t  the r e a c t i o n of d i m e t h y l s u l p h o x i d e .  which a l s o i n v o l v e s These workers found  t h a t complex a l c o h o l s ( n u c l e o s i d e d e r i v a t i v e s , s t e r o i d s ) were r a p i d l y and s e l e c t i v e l y o x i d i s e d to the aldehyde  (or ketone) on treatment  carbodlimide  (DCC)  corresponding  with N , N ' - d i c y c l o h e x y l -  and dimethylsulphoxide at room tempera-  t u r e , i n the presence  of c e r t a i n a c i d s .  prepared of the mixture  of (74)  and  A solution  (75)  was  (from the hydroxy-  m e t h y l a t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l ) i n dimethylsulphoxide c o n t a i n i n g a t r a c e of anhydrous phosphoric cess of DCC.  a c i d and an  A f t e r standing f o r one day at room  ex-  temperature,  d u r i n g which time a c r y s t a l l i n e p r e c i p i t a t e of N , N ' - d i c y c l o hexylurea formed and d i m e t h y l s u l p h i d e was t u r e was  evolved, the mix-  f i l t e r e d , d i l u t e d with ethanol and t r e a t e d w i t h  a hot e t h a n o l i c s o l u t i o n of 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e , as described previously. precipitated.  T h i s was  On d i l u t i n g with water a yellow c o l l e c t e d by f i l t r a t i o n and  from c o - p r e c i p i t a t e d N , N - d i c y c l o h e x y l u r e a 1  separated  by s o l u t i o n i n a  s m a l l volume of c h l o r o f o r m , i n which the urea was Examination  solid  Insoluble.  of the yellow product by t h i n l a y e r chromatography  - 1-35  -  r e v e a l e d the presence of two major components, which were i s o l a t e d "by chromatography on t h i c k p l a t e s of s i l i c a g e l , u s i n g m u l t i p l e development w i t h chloroform, and w i t h F r a c t i o n s X and Y, the  identified  2,4-dinitrophenylhydrazones  of the D-xylo- and D-lyxo- Isomers of 4 , 5 - d i - 0 - a c e t y l - 2 , 6 anhydro-3-deoxy-aldehydo-hexose r e s p e c t i v e l y , by m e l t i n g p o i n t and mixture m e l t i n g p o i n t , and t h i n l a y e r chromatography. The amount of mixed 2 , 4 - d i n i t r o p h e n y l h y d r a z o n e s t a i n e d by t h i s r e a c t i o n was  ob-  e q u i v a l e n t to the o x i d a t i o n of  approximately 35$ of the d i - O - a c e t y l - a n h y d r o d e o x y h e x i t o l s (74)  and  and about  (75)$  and comprised  about 60$ of the D-lyxo-  30$ of the D-xylo- d e r i v a t i v e  aldehydo-hexoses  That  the  thus I s o l a t e d were products of the o x i -  d a t i o n r e a c t i o n was experiments  (X).  (Y)  confirmed by running separate c o n t r o l  under the same c o n d i t i o n s , i n one of which the  hydroxymethylation were omitted.  product, and i n the other the c a r b o d i i m i d e ,  N e i t h e r of these gave d e r i v a t i v e s on  quent treatment"with 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e .  subse-  - 136  -  EXPERIMENTAL General  Considerations  High pressure r e a c t i o n s were c a r r i e d out u s i n g Aminco 2 ^ / i 6 " ganese s t e e l Md.).  o.d. Micro  S e r i e s r e a c t i o n v e s s e l of man-  (Americal Instrument Co.  Inc., S i l v e r  I n f r a r e d (I.R.) s p e c t r a were measured on  Elmer Model 21  and Model .137  photometers.  Nuclear  were recorded  at 60 Mo/s  (Sodium C h l o r i d e )  magnetic resonance  Spring,  Perkinspectro-  (n.m.r.) s p e c t r a  on a V a r i a n A 6 0 spectrometerJ  resonance p o s i t i o n s are recorded  i n ppm  s i l a n e as r e f e r e n c e , set at zero  ( e x t e r n a l w i t h DgO,  t e r n a l w i t h other s o l v e n t s ) . were measured on a V a r i a n D. Mc/s,  an  using a Heteronuclear  from t e t r a m e t h y l in-  Double resonance s p e c t r a P. spectrometer,  Decoupler  a l s o at  60  (Nuclear Magnetic  sonance S p e c i a l t i e s ) ; modules o p e r a t i n g at ca_ 9.2 were used to p r o v i d e the deuterium frequency.  Re-  Mc/s  Gas-liquid  p a r t i t i o n chromatography (GLPC) s e p a r a t i o n s were e f f e c t e d u s i n g an Aerograph "Autoprep" Model A-700 (Wilkens ment Co.  Instru-  I n c . ) , employing a column ( 1 0 ' x / ^ " ) °f 2 0 $ 1  S i l i c o n e G E - S F - Q 6 on f i r e b r i c k , at a temperature of 1 8 0 ° , w i t h helium minute:.  as the c a r r i e r gas  at a flow r a t e of 40  ml/  Samples were i n j e c t e d d i r e c t l y onto the column  u s i n g a 6"  needle.  Water-saturated  5$ e t h a n o l at room temperature was  1-butanol  containing  employed as s o l v e n t f o r  -137  -  paper p a r t i t i o n chromatography* R  p  r e f e r e n c e t o t h i s s o l v e n t system.  values recorded are w i t h P o l y o l s were  detectedSwIth  73 sodium p e r i o d a t e - S c h i f f reagent (TLC) was on p l a t e s o f S i l i c a  .  T h i n l a y e r chromatography  G e l G (acc. t o S t a h l ) , and  zones were l o c a t e d by s p r a y i n g w i t h the g e n e r a l purpose r e agent  o f s u l p h u r i c a c i d c o n t a i n i n g 5$ fuming n i t r i c  and h e a t i n g at 1 3 0 ° .  M e l t i n g p o i n t s were determined  K o f l e r b l o c k and are u n c o r r e c t e d .  Analyses were  i n the l a b o r a t o r i e s o f Dr. A. Bernhardt, Mulheim West Germany, and by the M i c r o a n a l y t i c a l U n i v e r s i t y of B r i t i s h  Columbia.  acid, on a  performed (Ruhr),  Laboratory,  -  138-  Experimental S e c t i o n A 3,4-Di-O-acetyl-D-xylal  (22)  In a 500 ml, 3-necked f l a s k equipped w i t h an s t i r r e r and a thermometer, a c e t i c anhydride (200 ml) c o o l e d t o 0° and 70$ p e r c h l o r i c a c i d dropwlse.  The s o l u t i o n was  and D-xylose  (50 g) was  (1.2 ml) was  efficient was  added  then warmed t o room temperature  added i n p o r t i o n s d u r i n g the course  of 1 hour t o the s t i r r e d mixture at such a r a t e t h a t the temperature d i d not r i s e above 3 0 ° . was  Red phosphorus  (15  g)  added a f t e r c o o l i n g the r e a c t i o n mixture t o below 20°  i n an i c e - w a t e r bath, f o l l o w e d by the dropwlse of bromine (30 ml) and then of water  (15  addition  ml) t o the con-  t i n u o u s l y s t i r r e d mixture w i t h c o n t r o l of temperature at or below 20°.  A f t e r s t a n d i n g at room temperature f o r 3  hours the r e a c t i o n mixture was  f i l t e r e d , and the  paper was  g l a c i a l acetic acid.  washed w i t h a l i t t l e  filter The  deep y e l l o w f i l t r a t e , c o n t a i n i n g 2 , 3 , 4 - t r l - Q - a c e t y l - c x - D x y l o p y r a n o s y l bromide, was  immediately added t o a r e d u c t i o n  mixture, p r e v i o u s l y prepared as f o l l o w s . sodium a c e t a t e t r l h y d r a t e g l a c i a l acetic acid dust  (200 g) i n water  (200 ml) was  A s o l u t i o n of (290 ml)  c o o l e d t o -10°, and  (110 g) and c u p r i c s u l p h a t e pentahydrate  i n water  (40 ml) were added.  and zinc  (11 g) d i s s o l v e d  When the b l u e c o l o u r had  dis-  appeared, the above s o l u t i o n of 2 , 3 , 4 - t r l - O - a c e t y l - o c - D -  x y l o p y r a n o s y l bromide was  139 -  g r a d u a l l y added over a p e r i o d of  1 hour t o the mixture, which was c o o l i n g i n an a c e t o n e - s o l i d COg  maintained at -10° bath, and which was  by vigor-  o u s l y s t i r r e d by an e f f i c i e n t H i r s c h b e r g - t y p e s t i r r e r . r i n g was  continued f o r a f u r t h e r 3 hours w i t h the  at - 1 0 ° ,  C e l i t e was  added, and the mixture was  Stir-  temperature  filtered  through a l a y e r of C e l i t e i n t o a s u c t i o n f l a s k c o n t a i n i n g ca 500 g of crushed i c e , fragments  of s o l i d carbon d i o x i d e  being added t o the mixture d u r i n g f i l t r a t i o n t o prevent undue r i s e i n temperature. aqueous a c e t i c a c i d  50$  A f t e r washing the f i l t e r w i t h c o l d (ca_ 150  ml), the f i l t r a t e was e x t r a c t e d  w i t h f i v e 100 ml p o r t i o n s of c o l d c h l o r o f o r m .  The  combined  c h l o r o f o r m e x t r a c t s were washed w i t h f i v e 100 ml p o r t i o n s of i c e - c o l d water, c o l d aqueous sodium carbonate u n t i l  free  of a c i d , three 100 ml p o r t i o n s of c o l d water, then d r i e d over anhydrous c a l c i u m c h l o r i d e , f i l t e r e d and  evaporated  under reduced p r e s s u r e t o a syrup, which was.  immediately  d i s t i l l e d under vacuum.  •  (26  The f r a c t i o n b.p.  115-120°/1.4  g) c r y s t a l l i s e d o v e r n i g h t i n the r e f r i g e r a t o r ,  -312°  (e, 2.3  methanol, 96^4  i n chloroform).  One  spot by TLC  s t r o n g band at 1640  v/v) > I.R.,  mm  22  Lpdp  (benzenecm~"  L  (C=G  stretching). Dicobalt  Octacarbonyl  A s l u r r y of c o b a l t  ( i i ) carbonate  (15  g) i n anhydrous  benzene (60 ml), c o n t a i n e d i n the Pyrex g l a s s l i n e r of a  - 140  -  h i g h p r e s s u r e r e a c t i o n v e s s e l was xide  (1600  p s i ) and hydrogen ( l 6 0 0 p s i ) at 180°  A f t e r c o o l i n g t o room temperature (combined p r e s s u r e about brown s o l u t i o n was carbonate.  shaken w i t h carbon monof o r 2 hours.  the unreacted  gases  2400 p s i ) were vented and the dark  f i l t e r e d to remove unreacted c o b a l t  The f i l t r a t e was  (II)  d i l u t e d w i t h an equal volume  of petroleum e t h e r (b.p. 30-60°), and on s t a n d i n g at  -10°  i n a w e l l stoppered f l a s k , orange c r y s t a l s of d i c o b a l t o c t a c a r b o n y l were p r e c i p i t a t e d , y i e l d about  10 g.  The  crystalline o  product c o u l d be s t o r e d under the mother l i q u o r s a t -10 s e v e r a l weeks without undue Hydroxymethylation  for  decomposition.  of 3,4-di-Q_-acetyl-D-xyla 1  T y p i c a l experimental c o n d i t i o n s f o r the a b s o r p t i o n of 3 moles of s y n t h e s i s gas were as f o l l o w s . of 3 * 4 - d i - 0 - a c e t y l - D - x y l a l (5.6  To a s o l u t i o n  g) i n anhydrous benzene  (25  m l ) , c o n t a i n e d i n the g l a s s l i n e r of a h i g h p r e s s u r e r e a c t i o n v e s s e l , was  added d i c o b a l t o c t a c a r b o n y l ( 1 . 5 g ) •  pered l i n e r was  The  stop-  then i n s e r t e d Into the a u t o c l a v e , which  f l u s h e d w i t h carbon monoxide.  Carbon monoxide was  was  then added  to a p r e s s u r e of 500 p s i , f o l l o w e d by hydrogen to a t o t a l p r e s s u r e of 3000 p s i , and the r e a c t a n t s were heated, r o c k i n g , at 125-13©° f o r about room temperature was  2 hours.  with  A f t e r c o o l i n g to  o v e r n i g h t , unreacted s y n t h e s i s gas pressure  r e l e a s e d and the dark c o l o u r e d s o l u t i o n was  transferred  - .141 to a short  (8 x 8 cm dlam.) column of F l o r i s i l ,  prepared as a s l u r r y i n anhydrous benzene. petroleum ether (b.p. 30-60°) was was  previously  E l u t i o n with  continued u n t i l  catalyst  completely removed and the e l u a t e was c o l o u r l e s s , and  the r e a c t i o n produet was then e l u t e d w i t h benzene-ethanol (10*1, v / v ) .  E v a p o r a t i o n of s o l v e n t under reduced pressure  gave a syrup:;- '($''*&/. g));c.o$s£|ping p r i n c i p a l l y of a mixture of 2 , 3 - d i - 0 - a c e t y l - l , 5 - a n h y d r o - 4 - d e o x y - h e x i t o l s . To the syrupy product (4.4 g) d i s s o l v e d i n anhydrous (50 ml) was added, w i t h c o o l i n g , a s o l u t i o n of  methanol  sodium ( 0 . 2 g) i n anhydrous methanol o was  set a s i d e at about 5  f o r 1 day.  (5© m l ) , and the mixture Fragments of s o l i d  carbon  d i o x i d e were then added u n t i l the s o l u t i o n was n e u t r a l to pH i n d i c a t o r paper, and s o l v e n t was removed under reduced pressure.  The r e s u l t i n g s o l i d r e s i d u e was d i s s o l v e d In  water (50 ml) and sodium ions were removed  by passage of  the s o l u t i o n through a column of Amberlite IR-120  (H )  c a t i o n exchange r e s i n , which was then washed w i t h  distilled  water.  volume  The combined e f f l u e n t and washings  (total  +  about 25© ml) were then reduced to a syrup (2.75 g) by e v a p o r a t i o n under reduced p r e s s u r e at about 45°. The p r o -  -1 duct, which e x h i b i t e d a strong band at around 3400 cm~ (0-H s t r e t c h i n g ) i n the i n f r a r e d , showed two main components on paper chromatography.  A p o r t i o n (0.40 g) of the deacety-  l a t e d mixture, d i s s o l v e d In a s m a l l volume of methanol, was  - 142 applied  e q u a l l y t o sijjp; sheets (57 x 46 cm) o f Whatman No. 1  f i l t e r paper, prepared f o r descending chromatography.  After  e q u i l i b r a t i o n and development f o r 40 hours, the two zones were l o c a t e d by spraying  t e s t s s t r i p s , cut from each sheet,  w i t h aqueous sodium p e r i o d a t e - S c h i f f extracted  reagent, and  separately  w i t h hot aqueous methanol ( i : i , v/v) t o a f f o r d  F r a c t i o n I ( 0 . 1 5 g ) , jR 0 . 4 7 , and F r a c t i o n I I ( 0 . 1 8 g ) , p  0.41.  R  p  " Characterisation  of F r a c t i o n s  I and I I  F r a c t i o n I (1,5-anhydro-4-deoxy-D-arablno-hexitol (44))  Fraction I, R was d i s s o l v e d  p  0 . 4 7 , i s o l a t e d by paper chromatography,  i n methanol, d e c o l o u r i s e d  by f i l t r a t i o n  through  a l a y e r o f G e l i t e - D a r c o 6 0 , and c r y s t a l l i s e d by the a d d i t i o n of i s o p r o p y l ether t o i n c i p i e n t t u r b i d i t y and cc'oling i n the r e f r i g e r a t o r .  R e c r y s t a l l i s a t i o n from the same r ~i ® o  solvents  2  gave a product, m.p. 1 0 2 ' , N.m.r. s i g n a l s 1.35  (DgO):  - 2.2 ppm ( 2 ) .  Found:  -13  LPClp  (e, ' 6 . 3 i n water) .  3.2 - 4.2 ( 7 ) ;  multiplet  Calc. f o r C H g  0^:  multiplet  C, 4 8 . 6 4 ; H, 8 . 1 6 .  C, 4 8 . 3 5 ; H, 8 . 1 0 .  1,5 - A n h y d r o - 4 - d e o x y - 2 , 3 , 6 - t r 1-0-p_-nit r obenz oy 1-Darabino-hexitol F r a c t i o n I (31 mg) and p - n i t r o b e n z o y l distilled,  330 mg) were d i s s o l v e d  chloride  i n anhydrous  (freshly  pyridine  - 143 (1 ml) and the s o l u t i o n was  -  heated at 80-90° f o r 1  A f t e r c o o l i n g , the mixture was  s t i r r e d with a s a t u r a t e d (5 ml) f o r  aqueous s o l u t i o n of sodium hydrogen carbonate 30 minutes.  hour.  The l i g h t c o l o u r e d s o l i d which separated  e x t r a c t e d w i t h c h l o r o f o r m , and the e x t r a c t was  was  washed w i t h  s a t u r a t e d sodium hydrogen carbonate s o l u t i o n and w i t h water, and d r i e d over magnesium s u l p h a t e . a syrup which c r y s t a l l i z e d from ether (b.p. 3 0 - 6 0 ° ) ; m.p. Calc. for 0  form).  e t h y l acetate-petroleum  215°;  0  H  Removal of s o l v e n t gave  ~ °° 5  (* c  1  ,  0  l  C, 5 4 . 6 0 ; H, 3.6©.  N :  n  c  h  l  o  Found:  27 21 13 3  C, 5 4 . 5 6 ; H,  3.86.  F r a c t i o n I I (1,5-anhydro-4-deoxy-L-xylo-hexitol  The component, R^ 0 . 4 l ,  was  obtained as a syrup,  a f t e r f i l t r a t i o n through c h a r c o a l , which c o u l d not crystallised.  (45))  be  P u r i f i c a t i o n by f o r m a t i o n of a c r y s t a l l i n e  t r i - O - a e e t y l d e r i v a t i v e , as d e s c r i b e d below, f o l l o w e d by d e a c e t y l a t i o n w i t h methanolic r n a c o l o u r l e s s syrup;  1.75 C  o  LP*Jj)  -44  ( D 0 ) : m u l t i p l e t 2.9  signals  2  - 2.2  (1);  sodium methoxide, a f f o r d e d  2 0  m u l t i p l e t 1.15  (c, 6.4  - 4.15 - 2.2  i n water).  N.m.r.  ( 7 ) > p a i r of q u a r t e t s ppm  (l).  Gale, f o r  6 12°4 > > ' « Pound: C, 4 8 . 3 6 ; H, 8 . 3 9 . 2,3*6-Tri-0-a c ety1-1,5-a nhydro-4-deoxy-L-xylo-hexitol H  :  C  4 8  6 4 j  H  8  l 6  F r a c t i o n I I (70 mg)  i n pyridine  ( l ml) and  acetic  r  °-  - 144 anhydride  ( l ml) was  heated  with e x c l u s i o n of moisture. temperature 50 m l ) .  -  f o r 20 minutes on a steam bath The  s o l u t i o n was  kept at room  o v e r n i g h t and then poured i n t o ice-water  A f t e r 1 hour the aqueous s o l u t i o n was  w i t h c h l o r o f o r m , which was  (about  extracted  s u c c e s s i v e l y washed with  5$  aqueous potassium hydrogen sulphate s o l u t i o n , s a t u r a t e d sodium hydrogen carbonate  s o l u t i o n and water, and  over magnesium s u l p h a t e .  Removal of s o l v e n t gave a syrup  (110 mg)  which soon c r y s t a l l i s e d .  ether-petroleum a c e t a t e ; m.p.  Recrystallisjation  from  e t h e r (b.p. 30-60°) a f f o r d e d the pure o 22  80-81  Calc. f o r C^H^O H,  dried  ;  :  [p{]  _ 4l°  (c, 0.8  C, 52.55? H, 6 . 6 2 .  tri-  i n chloroform).  Found:  C,  52.82;  6.58. Consumption of P e r i o d a t e Ion' Fraction I Absorbance readings at 223 myu. were measured at i n -  t e r v a l s on a Beckmann Model DU Spectrophotometer  (1 cm  c e l l s ) of an aqueous s o l u t i o n c o n t a i n i n g 0.439 x 10~^M F r a c t i o n I and 0.942 x 10 A).  Simultaneous  M of sodium p e r i o d a t e  silica of  (Reading  readings were made of a s o l u t i o n c o n t a i n i n g  0.439 x 10""^M of F r a c t i o n I o n l y (B), and of a s o l u t i o n t a i n i n g 0.942 x 10~^M values were o b t a i n e d :  of sodium p e r i o d a t e ( C ) .  con-  The f o l l o w i n g  - 145  (B C)-A< )  Time (hrs)  (B C ) - A W  a  C  0  Moles p e r i o d a t e / moleV s u b s t r a t e .  1.5  0.142  0.150  0.32  3.5  0.207  0.218  0.47  11.5  0.399  0.420  0.90  22  0.381  0.401  0.86  (a) :  decrease In absorbance due t o consumption o f p e r i o d a t e  (b) :  f r a c t i o n of known amount of p e r i o d a t e  consumed  Fraction II In a s i m i l a r manner, absorbances of s o l u t i o n s -4 -4 0.453 x 10 M with r e s p e c t t o F r a c t i o n I I and 0.942 x 10 M w i t h r e s p e c t t o p e r i o d a t e i o n were measured, to g i v e the following  values:  Time (hrs) .  (B C ) - A ( ) a  ,(B C)-A(to) C  o  Moles p e r i o d a t e / mole s u b s t r a t e  1.5  0.177  0.192  0.40  3.0  0.263  0.284  0.59  10.5  0.423  0.457  0.95  24  0.392  0.424  0.88  - 146 _ Enantiomeric  2-deoxy-3-0-(2-hydroxyethyl)-glycero-tetritols  F r a c t i o n I , Rp 0 . 4 7 (47 mg) was d i s s o l v e d eous s o l u t i o n  (5 ml) c o n t a i n i n g  periodic acid  excess) and immediately t r a n s f e r r e d which was p r o t e c t e d the  from l i g h t .  In an aqu-  (150 mg, 5C#  t o a p o l a r i m e t e r tube  The o p t i c a l r o t a t i o n o f  s o l u t i o n r a p i d l y assumed a constant v a l u e .  hours the s o l u t i o n was removed from the tube,  After 6 neutralised  by t h e a d d i t i o n o f excess barium carbonate, and f i l t e r e d i n t o a s o l u t i o n o f sodium borohydride (5© mg) i n water (3 ml).  A f t e r s t a n d i n g a t room temperature f o r 1 "Vg hours  the  s o l u t i o n was made s l i g h t l y a c i d t o pH i n d i c a t o r paper  by the dropwlse a d d i t i o n o f a c e t i c a c i d , Amberlite IR-120 (H ) +  r e s i n (5 ml) was then added, and the mixture was  r e d f o r 1 hour.  stir-  F i l t r a t i o n and e v a p o r a t i o n under reduced  p r e s s u r e gave a s o l i d r e s i d u e ,  which was r e p e a t e d l y eva-  porated w i t h methanol t o remove borate i o n as the methyl ester.  The r e s u l t i n g t r i o l ether ( I I I )  (44 mg) was a  syrup; L°<]jp - 1 9 ° ( c , 2 . 0 i n water); n.m.r. s i g n a l s multiplet plet  (D 0) : 2  3 . 5 - 3 . 9 , w i t h sharp s i g n a l at 3.72 ( 9 ) ; m u l t i -  (apparent q u a r t e t ) 3/fji" - 2 . 0 ppm ( 2 ) . The  t r i o l ether ( i l l ) was c h a r a c t e r i s e d  p-nitrobenzoyl  derivatives  at 90° w i t h p - n i t r o b e n z o y l pyridine  a portion chloride  ( 0 . 6 ml) f o r l h o u r .  as t h e t r i s -  (18 mg) was heated  (160 mg) i n anhydrous  Removal of excess p - n i t r o -  - 147 benzoyl c h l o r i d e and p y r i d i n e by s t i r r i n g w i t h s a t u r a t e d sodium hydrogen carbonate  s o l u t i o n , e x t r a c t i o n with c h l o r o -  form, washing with sodium hydrogen sulphate s o l u t i o n , sodium hydrogen carbonate  s o l u t i o n and water, d r y i n g over magnesium  sulphate and removal o f s o l v e n t gave a syrup  (80 mg) which  was c r y s t a l l i s e d from e t h y l acetate-petroleum  ether (b.p.  22 30-60°) ; m.p. 1 0 2 - 1 0 3 ° ; M -28° ( c , 1.1 C a l c . f o r C H 0 N : C, 5 4 . 3 0 ; H, 3 - 9 9 . <o 13 3  i n chloroform). Found: C,  D  o 7  o o  5 4 . 5 7 ; H, 3 . 9 5 .  The m e l t i n g p o i n t o f t h i s d e r i v a t i v e was  undepressed on admixture w i t h the corresponding d e r i v a t i v e of the t r i o l  ether o b t a i n e d , by a s i m i l a r procedure  t o the  above, from the p o l y o l s i s o l a t e d from the h y d r o g e n o l y s i s products  o f methyl  CX-D-glucopyranoside  82  F r a c t i o n I I , R„ 0 . 4 l , (3© mg) was converted by p e r i o date o x i d a t i o n and sodium borohydride above t o a t r i o l (c, 1.7  ether (IV) (27 mg), which had  |jx] ^  +17  In water); n.m.r. spectrum i d e n t i c a l w i t h t h a t de-  s c r i b e d above f o r t r i o l portion  r e d u c t i o n as d e s c r i b e d  (13 mg) o f t r i o l  converted  ether ( I I I ) from F r a c t i o n I . A ether (IV) from F r a c t i o n I I was  t o a t r i s - p - n i t r o b e n z o y l d e r i v a t i v e on h e a t i n g  w i t h p - n i t r o b e n z o y l c h l o r i d e ( 0 . 1 3 g) i n p y r i d i n e ( 0 . 5 m l ) , and i s o l a t e d i n the u s u a l way; the product s t a l l i s a t i o n from e t h y l acetate-petroleum 60°)  had m.p. 1 0 2 - 1 0 3 ° ;  [p<l^  (55 mg) on c r y ether  +26° ( c , 1.4  (b.p. 3 0 -  i n chloroform);  - 148 i n f r a r e d spectrum i d e n t i c a l w i t h that of the t r i s - p - n i t r o benzoate of t r i o l ether ( I I I ) . 0,  5 4 . 3 0 ; H, 3 . 9 9 .  Pound:  c,  Calc. f o r 2 7 2 3 ° 1 3 3 C  5 4 . 6 3 ) H,  H  H  4.09.  2-Deoxy-3-0-(2-hydroxyethy1)-L-glycero-tetr11ol  3,4,6-Tri-O-acetyl-D-galactal  i n anhydrous  (approximately 0.01  (40)(7 g) was  N) of sodium  dissolved  methoxide  methanol, and the s o l u t i o n was kept at room  temperature f o r 48 hours.  Removal of s o l v e n t  p r e s s u r e gave a syrup, from which D - g a l a c t a l  under reduced was  isolated  as white c r y s t a l s on e x t r a c t i o n w i t h b o i l i n g e t h y l R e c r y s t a l l i S a t i o n from the same s o l v e n t  m.p.  acetate.  gave ( 1 9 ) ( 2 . 5 g ) ,  100-102°. Methyl 2-deoxy-<x-D-galactopyranoside To a s o l u t i o n of D - g a l a c t a l  methanol  (22.5  ml) was  c h l o r i d e i n methanol was  (49)  (19)  D-Oalactal  in a solution  :  transferred  added a 2% (w/v)  (2.5  ml).  g) i n anhydrous s o l u t i o n of hydrogen  A p o r t i o n of the s o l u t i o n  to a 2 dm p o l a r i m e t e r tube and the change  i n o p t i c a l r o t a t i o n was change was  (2.5  (55)  observed at i n t e r v a l s ; no  further  observed a f t e r 90 minutes from the a d d i t i o n of  hydrogen c h l o r i d e .  A f t e r 2 hours the recombined  solutions  were n e u t r a l i s e d by the a d d i t i o n of s i l v e r carbonate, f i l t e r e d and evaporated t o a syrup (2.7  g).  Addition  of a s m a l l volume  - i4 9 of acetone r e s u l t e d In the s e p a r a t i o n of c r y s t a l s which were i s o l a t e d and r e c r y s t a l l i s e d from e t h y l a c e t a t e ; 1.0  g;  m.p.  112-114°. Methyl 3,6-anhydro-2-deoxy-oc-D-galaetopyranoside  (57)  To an i c e - c o l d , s t i r r e d s o l u t i o n of methyl 2-deoxyoc-D-galactopyranoslde ( 1 . 0 g) In anhydrous  pyridine, a  c o o l e d s o l u t i o n of p - t o l u e n e s u l p h o n y l c h l o r i d e anhydrous  pyridine  (4 ml) was  minutes, and the mixture was Water ( 0 . 5  ml) was  added over a p e r i o d of 50 set a s i d e at 0° f o r 20 hours. 0°,  added to the s t i r r e d s o l u t i o n a t  which a f t e r 30 minutes was ml).  ( l . O g) i n  The mixture was  then poured i n t o i c e - w a t e r  (100  e x t r a c t e d w i t h c h l o r o f o r m , and the  combined e x t r a c t s were washed with potassium hydrogen phate s o l u t i o n , sodium hydrogen  sul-  carbonate s o l u t i o n and  water,  d r i e d over magnesium s u l p h a t e , f i l t e r e d and evaporated t o a syrup (56)  (1.46  g).  T h i s was  d i s s o l v e d i n ethanol  ml); measurement of the o p t i c a l r o t a t i o n of t h i s gave a v a l u e of  Qcxfljp  + 93°  6-0_-p-tolylsulphonyl d e r i v a t i v e e t h a n o l i c s o l u t i o n was (4.3  ( c , 2.6 (56).  (53  solution  i n ethanol) f o r the To the  recombined  added IN sodium hydroxide s o l u t i o n  m l ) , and the s o l u t i o n was  heated at 60°  for 1  hour,  n e u t r a l i s e d w i t h s o l i d carbon d i o x i d e and evaporated t o dryness.  The product was  repeatedly extracted with b o i l i n g  acetone and a f t e r removal of s o l v e n t under reduced pressure  - 150 the  r e s i d u e was r e d i s s o l v e d In e t h y l a c e t a t e .  Filtration  and e v a p o r a t i o n of s o l v e n t gave a syrup (O.65 g ) , which distilled  at 130°  (bath t e m p e r a t u r e ) / 0 . 1 mm as a c o l o u r l e s s  l i q u i d which soon c r y s t a l l i s e d ; y i e l d 0.47  anhydro-2-deoxy-oc-D-galactopyranoside (57)* o 1— -124 crystallised  from e t h e r ; m.p.  76-77  > L°<J  3,6-  g o f methyl  D  which was r e o +94  (0,  5.7  i n water). 3,6-Anhydro-2-deoxy-D-lyxo-hexose  (58)  To a s o l u t i o n of the methyl g l y c o s i d e  (57)  (0.28  i n water ( 6 . 0 ml) was added 2N s u l p h u r i c a c i d s o l u t i o n ml),  and the mixture was  f o r 110  minutes.  filtration  g) (0.6  l e f t stand at room temperature  N e u t r a l i s a t i o n w i t h barium carbonate,  and removal of water by f r e e z e - d r y i n g gave a  c o l o u r l e s s syrup, which was r e d i s s o l v e d i n water, f i l t e r e d , and again evaporated by f r e e z e - d r y i n g .  The r e s i d u e  was  d i s s o l v e d i n warm acetone, f i l t e r e d and evaporated under reduced p r e s s u r e t o a c l e a r , c o l o u r l e s s syrup. 3,6-anhydro-2-deoxy-D-lyxo-hexose, (c, 5 . 1  In w a t e r ) .  peak at 1715  cm  -1  Y i e l d of  0.26 g j • LPdp  +25°  I.R. spectrum ( l i q u i d f i l m ) :  sharp  (aldehyde C=0  stretching).  1,4-Anhydro-5-deoxy-D-arabino-hexitol  (59)  To a s o l u t i o n of the anhydro-sugar (58)  (95 mg) i n  water ( l . O ml) was added dropwise a s o l u t i o n of sodium  - 151  -  (5© mg) In water ( 1 . 0 m l ) . A f t e r 1 hour, Amber-  borohydride  l i t e IR-120 (H ) r e s i n was added i n s m a l l p o r t i o n s u n t i l +  Jiydrogen was no longer evolved; more r e s i n  (ca_ 3 ml) was  then added and the mixture was s t i r r e d f o r 30 minutes. F i l t r a t i o n and e v a p o r a t i o n under reduced  pressure gave a  s o l i d r e s i d u e which was r e p e a t e d l y evaporated  with methanol  to a f f o r d 1,4-anhydro-5-deoxy-D-arabino-hexitol c o l o u r l e s s syrup The  Qoc]|p +21°  (86 mg);  anhydrodeoxyhexitol  ( c , 1.7  (59) as a i n ethanol).  was c h a r a c t e r i s e d as the t r i s - p -  nitrobenzoyl derivative. 1,4-Anhydro-5-deoxy-2,3,6-tri-0-p-nitrobenzoyl-Darabino-hexitol A p o r t i o n (25 mg) of (59) was heated with  p-nitro-  b e n z o y l c h l o r i d e ( 0 . 2 5 g) i n p y r i d i n e ( 0 . 7 ml) and the product was i s o l a t e d i n the u s u a l way.  The r e s u l t i n g  (114 mg) c r y s t a l l i s e d from chloroform-petroleum 3 0 - 6 0 ° ) ; m.p. 1 5 9 - 1 6 0 ° ; Calc. f o r C 7 21°13 3 2  H  N  :  M  D  -96  syrup  ether (b.p.  (c, 0.7 i n chloroform).  °> 54.46; H, 3 - 5 6 .  Found:  C, 5 4 . 6 1 ;  H, 3 . 8 6 . 2-Deoxy-3-0-(2-hydroxyethyl)-L-glycero-tetrltol  (49)  1,4-Anhydro-5-deoxy-D-arabino-hexitol (59)(55 mg) was d i s s o l v e d i n a s o l u t i o n of p e r i o d i c a c i d  (96 mg, 1.3  moles)  - 152 In  water ( 5 . 0 m l ) . The s o l u t i o n was t r a n s f e r r e d t o a p o l a r l -  meter tube p r o t e c t e d from l i g h t and i t s r o t a t i o n was at  observed  i n t e r v a l s and found t o be constant a f t e r 3 "Vg ° u r s . h  A f t e r s t a n d i n g i n the dark o v e r n i g h t the s o l u t i o n was neut r a l i s e d w i t h barium  carbonate and then f i l t e r e d  s o l u t i o n o f sodium borohydride A f t e r 2 hours  into a  (70 mg) i n water (4 m l ) .  the s o l u t i o n was n e u t r a l i s e d w i t h a c e t i c  d e i o n i s e d by s t i r r i n g w i t h Amberllte I R - 1 2 0 ( H )  resin,  +  f i l t e r e d and evaporated under reduced  acid,  pressure to a residue  which was r e p e a t e d l y evaporated w i t h methanol t o a f f o r d a (51 mg),  syrup  spectrum ether  +17°  ( c , 2 . 0 i n w a t e r ) , whose n.m.r.  (DgO) was i d e n t i c a l w i t h t h a t d e s c r i b e d f o r t r i o l  (ill),  and w i t h t h a t o f t r i o l  A portion  ether ( I V ) .  (30 mg) o f (49) was converted t o a t r i s -  p - n i t r o b e n z o y l d e r i v a t i v e i n the u s u a l way.  Crystallisation  from e t h y l a c e t a t e - p e t r o l e u m e t h e r (b.p. 30-60°) product,  r "i 2 4 LP<JD  + 2  7  o  \ • i n c h l o r o f o r m ) , whose m e l t i n g  ( c , 1.1  p o i n t o f 1 0 1 - 1 0 2 ° was undepressed p - n i t r o b e n z o a t e o f the t r i o l II.  gave a  on admixture  w i t h the t r i s -  e t h e r (IV) d e r i v e d from  Fraction  The i n f r a r e d s p e c t r a o f both n i t r o b e n z o a t e s were i d e n -  tical.  Calc. f o r C Y H 2  C, 5 4 . 6 i ; H , 4 . 0 0 .  2 3  0  1 3  N : 3  C, 54.30? H , 3 . 9 9 .  Found:  - 153  -  Attempted p r e p a r a t i o n s of 2 - d e o x y - 3 , 4 - d i - 0 - a c e t y l D-xylopyranosyl  (a)  cyanide  By a d d i t i o n of HCN  Hydrogen cyanide was  to 3 , 4 - d i - O - a c e t y l - D - x y l a l  generated by a d d i t i o n of a s a t u r a t e d  s o l u t i o n of sodium cyanide to 50$ s u l p h u r i c a c i d the gas was  (22).  solution  c h l o r i d e tubes surrounded  o  by water at 3 0 - 4 0 , and then  densed i n t o a 50 ml f l a s k , p r o t e c t e d from atmospheric c o n t a i n i n g 3 , 4 - d i - 0 _ - a c e t y l - D - x y l a l (0.52  i c e - s a l t mixture. the f l a s k was  conmoisture,  g) and sodium cya-  nide (10-15 mg)-, by passage through a . c o i l surrounded  was  ;  d r i e d by passage through a s e r i e s of c a l c i u m i  t i o n was  1 0 0  by an  A f t e r the a d d i t i o n of about 5 ml of  HCN,  s e a l e d by a c a l c i u m c h l o r i d e tube, -the s o l u -  s t i r r e d at 0  f o r 5 hours, and the hydrogen cyanide  then allowed to evaporate o v e r n i g h t .  of the r e s i d u a l syrup was  The I,R.  spectrum  unchanged from t h a t of 3 , 4 - d i - 0 -  acetyl-D-xyla1. (b)  By r e a c t i o n of 3 , 4 - d i - 0 - a c e t y l - D - x y l o p y r a n o s y l c h l o r i d e  with Hg(CN) . 2  3,4-Di-0-acetyl-D-xyl&pyranosyl chloride  a c o o l e d s o l u t i o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l (2.5 hydrous benzene (20 ml) was chloride.  (67):  g) In an-  s a t u r a t e d w i t h dry hydrogen  A f t e r s t a n d i n g f o r 1 hour, the s o l v e n t was  moved under reduced p r e s s u r e at 30°  re-  to g i v e a c o l o u r l e s s o i l .  - 154 I,R|. spectrum ( l i q u i d film)*, at  1640  cm"  1  (C=C  -  disappearance of a b s o r p t i o n  stretching).  To a s o l u t i o n of ( 6 7 ) ( 1 . 5 g) In anhydrous nitromethane (5 ml) was was  added mercuric cyanide (1.7  g) * and the mixture  s t i r r e d at room temperature f o r 24 hours w i t h e x c l u s i o n  of m o i s t u r e .  The dark c o l o u r e d s o l u t i o n was  volume under vacuum, methanol t u r e was  poured i n t o water  sodium c h l o r i d e  (2.5  g).  (15  reduced i n  ml) was added and the mix-  (40 ml) and i c e (30 g) c o n t a i n i n g E x t r a c t i o n w i t h c h l o r o f o r m , wash-  ing w i t h water, d r y i n g over sodium sulphate and e v a p o r a t i o n of s o l v e n t gave a dark brown syrup, which was  chromatographed  through a column of n e u t r a l alumina u s i n g benzene-ether(70*-30'l, v/v) as d e v e l o p i n g s o l v e n t to a f f o r d a  methanol  n e a r l y c o l o u r l e s s syrup. v/v)i  complex  mixture*  a b s o r p t i o n i n 2000-2300 mately  T.L.C. (benzene-methanol,  I.R.  spectrum ( l i q u i d f i l m ) ;  cm  r e g i o n (C=N)*  N,  96"4 no  approxi-  2.6$. In a s i m i l a r experiment, a s o l u t i o n of ( 6 7 ) ( l . l (7 ml) was  i n anhydrous benzene  added dropwise t o a r e -  f l u x i n g suspension of s i l v e r cyanide ( 0 . 7 e t h e r (15  ml).  g)  g) i n anhydrous  A f t e r 5 hours the mixture was  cooled, f i l t e r e d  and evaporated to a syrup which c o n s i s t e d of a mixture of unreacted  (67)  and 3 , 4 - d i - O - a c e t y l - D - x y l a l  I.R. band at 1640  cm , -1  and T . L . C ) .  (identified  by  - 155 2 , 3 - D l - 0 - a c e t y 1 - 1 , 5 -a (70) and  hexltol  nhydro-4,6-dideoxy-B-arablno-  2,3-dl-0-acetyl-1,5-anhydro-4,6-  dideoxy-L- x y l o - h e x l t b l (71)  (a,)  :  By r e a c t i o n of (67) w i t h methyl magnesium "bromide.  To a s t i r r e d s o l u t i o n o f methyl magnesium bromide i n d r y e t h e r , prepared by t h e slow a d d i t i o n of methyl bromide gas to a s t i r r e d suspension o f magnesium ( 3 . 2 g) i n d r y ether (50 ml), under an atmosphere o f n i t r o g e n , was added dropwise over 45 minutes a s o l u t i o n o f 3 , 4 - d i - 0 - a c e t y l - 2 - d e o x y D-xylopyranosyl c h l o r i d e  (prepared by the a d d i t i o n of hydrogen  c h l o r i d e t o 3 , 4 - d i - O - a c e t y l - D - x y l a l ( 2 . 5 g) as d e s c r i b e d above) i n d r y e t h e r (30 m l ) .  A f t e r r e f l u x i n g f o r 5 hours,  the s o l u t i o n was c o o l e d and added s l o w l y t o a mixture of i c e and water (approximately 750 ml) c o n t a i n i n g a c e t i c (5 m l ) .  The aqueous phase was f i l t e r e d through  acid  Celite,  n e u t r a l i s e d w i t h 2N NaOH s o l u t i o n , and evaporated t o a white solid.  The r e a c t i o n product was separated from Inorganic  m a t e r i a l by repeated e x t r a c t i o n , f i l t r a t i o n and e v a p o r a t i o n w i t h e t h a n o l , and subsequently w i t h acetone, t o y i e l d a yellow syrup  (0.95 g)•  Paper chromatography showed one zone  (Rp O.69) on s p r a y i n g w i t h p e r i o d a t e - S c h i f f reagent. p o r t i o n o f t h e product  ( 0 . 3 3 g) was p u r i f i e d by chromatography  on paper t o g i v e a mixture (70)  and ( 7 1 ) .  A  ( 0 . 2 2 g) o f anhydrodideoxyhexitols  N.m.r. s i g n a l s  ( D O ) : complex m u l t i p l e t  - 156 . 3.0 - 4.2 ( 5 ) " m u l t i p l e t u p - f i e l d from 2.2 ( 2 ) , C-CH -C; 0  p a i r o f o v e r l a p p i n g doublets ( J = 6 c/s) at 1.14 and 1.17 Ppm ( 3 ) , C-CH . 3  A p o r t i o n of the p u r i f i e d mixture of (70) and (71) (100 mg) was a c e t y l a t e d w i t h a c e t i c anhydride ( l ml) and pyridine  ( l ml) at room temperature o v e r n i g h t .  of the product i n the u s u a l way gave a syrup  Isolation  (110 mg)  which was f r a c t i o n a t e d by GLPC to y i e l d two pure components (72)  and (73)* the l a t t e r being i d e n t i f i e d as 2 , 3 - d l - 0 -  acety .1 - 1 , 5 - a n h y d r o - 4 , 6 - d i d e o x y - L - x y l o - h e x i t o l by independent s y n t h e s i s from 1 , 5 - a n h y d r o - 4 - d e o x y - L - x y l o - h e x i t o l (45) as d e s c r i b e d below. 2,3-Di-0-a c ety1-1,5-anhydro-4,6-dideoxy-D-arabinohexitol  (72)>  liquid; c  10 l6°5 H  r e l a t i v e r e t e n t i o n time 1.10" c o l o u r l e s s  11°^^ " :  8 2  ° (°*  1  ,  0  l  n  °V 5 5 . 5 4 ; H, 7.46.  N.m.r. s i g n a l s  (CCl^) :  chloroform). Calc. f o r Pound:  C, 55.61s H, 7 . 5 5 .  m u l t i p l e t s a t 4.75 - 5.0 ( 2 ) , 4 . 4 -  4.65  ( 1 ) , 3 . 3 5 - 3 . 9 ( 3 ) ; two sharp s i g n a l s at 2.02 (3) and  2.06  ( 3 ) , -0C0CH ; m u l t i p l e t 1 . 5 - 1.85 ( 2 ) , C-CH -C; doublet 0  3  d  (J = 6 c/s) 1.13  ppm ( 3 ) , C-CH_. ~> i 2,3-Di-0-a c ety1-1,5-a n h y d r o - 4 , 6 - d i d e o x y - L -x y l o - h e x i t o l  (73) r e l a t i v e r e t e n t i o n time 1.00; c o l o u r l e s s l i q u i d ; r ~i 24 L°y -21°(c , 0 . 9 i n c h l o r o f o r m ) . C a l c . f o r C ^ ^ g O ^ : :  D  C,  -  5 5 . 5 4 J  H, 7.46.  (GCl^): 3.65  Found:  multiplets  C,  157  5 5 . 4 7  -  ;  H, 7.42.  a t 4 . 6 5 - 5.0.(2), 3-8 - 4 . 2 ( l ) a n d . 3 . 0 -  ( 3 ) : sharp s i g n a l a t 1 . 9 7 ( 6 ) , -OCOCH^,  on m u l t i p l e t (3),C-CH (73)  N.m.r. s i g n a l s  ( 2 ) , C-CRg-C: doublet  superimposed  ( J = 6 c/s) 1.20 ppm  . from 1 , 5 - a n h y d r o - 4 - d e o x y - L - x y l o - h e x i t o l ( 4 5 )  To ah i c e - c o l d s o l u t i o n o f ( 4 5 ) ( 7 0 mg) i n anhydrous pyridine  ( 0 . 5 ml) was added over 2 0 minutes a s o l u t i o n of  p-toluenesulphonyl chloride pyridine  ( 1 . 0 ml).  ( l © 5 mg, 1 . 1 moles) i n anhydrous  A f t e r 1 8 hours a t 5 ° , a c e t i c  anhydride  ( 1 . 0 ml) was added and t h e mixture was stood f o r a f u r t h e r 1 2 hours a t room temperature.  I s o l a t i o n of the product i n  the u s u a l manner gave a syrup  (140 mg) which c o n t a i n e d  approximately 80$ o f 2 , 3 - d l - 0 - a c e t y l - . 1 , 5 - a n h y d r o - 4 - d e o x y — 6-0-p-tolylsulphonyl-L-xylo-hexitol  ( 7 7 ) , as judged by t h e  amount of sodium p-toluenesulphonate l i b e r a t e d therefrom,The  crude product i n acetone  iodide  ( 2 ml) was heated w i t h sodium  (140 mg) i n a s e a l e d tube a t 1 0 0 ° f o r 3 hours.  cooling,  sodium p-toluenesulphonate  After  ( 5 8 mg) was removed by  f i l t r a t i o n and the s o l u t i o n was evaporated under reduced pressure to a s o l i d residue  Extraction  and e v a p o r a t i o n o f s o l v e n t gave a syrup 6-deoxy-6-iodo-derivative ml)  w i t h r e f l u x i n g ether ( 1 2 5 mg)•  ( 7 9 ) was d i s s o l v e d  c o n t a i n i n g 5N sodium hydroxide s o l u t i o n  The crude  i n methanol (.10 ( 0 . 5 m l ) , and  - 158  -  shaken w i t h hydrogen at atmospheric (15  i n the presence of Raney n i c k e l  p r e s s u r e and f o r 30  mg)  temperature  minutes.  F i l t r a t i o n , n e u t r a l i s a t i o n w i t h s o l i d carbon d i o x i d e and e v a p o r a t i o n under reduced pressure gave a white s o l i d , which was  a c e t y l a t e d by h e a t i n g at 100°  anhydride  f o r 3 hours w i t h a c e t i c  (2 ml) and anhydrous sodium a c e t a t e (0.4  g).  Iso-  l a t i o n of the product i n the u s u a l way  gave  2,3-dl-0-acetyl-  l,5-anhydro-r4,6-dideoxy-L-xylo-hexitol  (73)  as a syrup  mg), was  which showed one zone on GLPC whose r e t e n t i o n  time  i d e n t i c a l w i t h the faster-moving component of the mixture  of a c e t a t e s prepared as d e s c r i b e d above.  The  infrared  trum of a p o r t i o n of the product thus p u r i f i e d by GLPC i d e n t i c a l w i t h t h a t of the l a t t e r zone, which was  From (74)  and  (75)  specwas  thus  (73).  i d e n t i f i e d as the L - x y l o isomer (b)  (50  obtained by r e a c t i o n of 3,4-di-O-  a c e t y l - D - x y l a l w i t h carbon monoxide and hydrogen  3,4-Di-O-acetyl-D-xylal (25  ml) was  hydrogen  (5.6  g) i n anhydrous benzene  r e a c t e d w i t h carbon monoxide (1100  (2200  p s i ) at  130°  d i c o b a l t o c t a c a r b o n y l (1.5  for  3  p s i ) and  hours i n the presence  g)'» and the product was  of  separated  from c a t a l y s t as p r e v i o u s l y d e s c r i b e d to g i v e a syrup (6.1  g)  c o n s i s t i n g c h i e f l y of two  i s o m e r i c 2,3-di-0-acety1-1,|-anhydro-  4-deoxy-hexitols  (75).  (1.5  g) was  (74)  and  A p o r t i o n of the product  d e a c e t y l a t e d w i t h methanollc  sodium methoxide.  -, m I s o l a t i o n i n the u s u a l way paper chromatography hexitol  -  and f r a c t i o n a t i o n by p r e p a r a t i v e  gave 1,5  -anhydro-4-deoxy-D-arabino-  (44) and 1,5-anhydro-4-deoxy-L-xylo-hexitol (45),  i d e n t i c a l w i t h the f r a c t i o n s o b t a i n e d i n a p r e v i o u s experiment . To a f u r t h e r p o r t i o n of the oxo product (1.5 g) i n anhydrous chloride  pyridine  (1.8 g).  (6 ml) was  added p - t o l u e n e s u l p h o n y l  A f t e r s t a n d i n g at room temperature f o r  18 hours the product was  i s o l a t e d i n the u s u a l manner to  y i e l d a syrup (1.6 g) whose n.m.r. spectrum i n d i c a t e d  approxi-  mately 75$ of 2,3-di-0-acetyl-1,5-anhydro-4-deoxy-6-0-t(ptolylsulphonyl)-hexitols product iodide  ((76)  (1.5 g) i n acetone  + ( 7 7 ) ) to be p r e s e n t .  (12 ml) was  heated w i t h sodium  (1.5 g) at 100° f o r 3 hours i n a s e a l e d tube.  c o o l i n g , sodium p-toluenesulphonate (0.52 g) was by f i l t r a t i o n ,  the f i l t r a t e was  The  After  removed  evaporated to dryness and  repeatedly extracted with b o i l i n g ether.  The crude mixture  of 2 , 3 - d i - 0 - a c e t y l - l , 5 - a n h y d r o - 4 , 6 - d i d e o x y - 6 - i o d o - h e x i t o l s ((78)  +• (79)) (1.0 g) was  dissolved  t a i n i n g 5N sodium hydroxide s o l u t i o n  i n methanol  (40 ml)  con-  (2 m l ) , and shaken w i t h  hydrogen at atmospheric p r e s s u r e and temperature i n the presence of Raney n i c k e l (100 mg) sorption  of hydrogen  (46 ml) was  f o r 30 minutes, when abcomplete.  After standing  at room temperature f o r 2 hours the s o l u t i o n was  filtered,  n e u t r a l i s e d w i t h s o l i d carbon d i o x i d e and evaporated t o a white s o l i d .  Repeated e x t r a c t i o n , f i l t r a t i o n  and e v a p o r a t i o n w i t h  - 160; i acetone gave a pale yellow syrup, which was f u r t h e r  purified  by p r e p a r a t i v e paper chromatography to y i e l d a c o l o u r l e s s syrup R  p  (0.20 g)J one zone on paper chromatography of i d e n t i c a l  value  (O.69) t o the mixture  ((70) + (71)) p r e v i o u s l y ob-  t a i n e d by r e a c t i o n of (67) w i t h methyl magnesium bromide. N.m.r. spectrum  (D 0): 2  e s s e n t i a l l y i d e n t i c a l with t h a t  d e s c r i b e d above f o r the mixture  o f anhydrodideoxyhexitols  (70) and (71). A p o r t i o n of the p u r i f i e d product l a t e d w i t h a c e t i c anhydride-sodium  (110 mg) was a c e t y -  a c e t a t e t o y i e l d a syrup  (140 mg) which was f r a c t i o n a t e d by GLPC i n t o  (74) and (75),  i d e n t i c a l w i t h the two f r a c t i o n s i s o l a t e d as d e s c r i b e d above on the b a s i s o f r e t e n t i o n times, s p e c i f i c r o t a t i o n s ( B x j § ^ -81° and - 2 3 ° r e s p e c t i v e l y and  (c, 1 . 2 i n c h l o r o f o r m ) ) , and n.m.r,  infrared spectra. I d e n t i f i c a t i o n of "Polyol Y" from Hydrogenolysis of Methyl  Oc-D-glucopyranoside  80 82 '  The t r i s - p - n i t r o b e n z o a t e o f t h i s compound (170 mg), k i n d l y s u p p l i e d by Dr. P. A. J . G o r i n , was debenzoylated by r e f l u x i n g with 0.1N methanollc f o r 1 hour. and  sodium methoxide (30 ml)  F i l t r a t i o n t o remove methyl p - n i t r o b e n z o a t e ,  i s o l a t i o n of the product  i n the u s u a l way gave a c o l o u r -  22 (38 mg) i  + 4 0 ° (c, 2 . 2 i n water), ( p r e v i o u s l y 82 . J . r e p o r t e d value was +19 ) . N.m.r. s i g n a l s (p^0) • m u l t i p l e t 2 . 9 - 4.15 ( 7 ) ; p a i r of q u a r t e t s centered around 2 . 0 l e s s syrup  0  -  161  -  ( l ) J m u l t i p l e t ca_ 35 c/s wide centered around 1.5 The  spectrum was  ppm  (l) .  I d e n t i c a l with that of 1 , 5 - a n h y d r o - 4 (45).  deoxy-L-xylo-hexitol  2 , 3 , 6 - T r 1 - 0 - a c e t y 1 - 1 , 5 - a nhydro-4-de o x y - D - x y l o - h e x i t o l The  anhydrodeoxyhexitol  as d e s c r i b e d above was  obtained on  a c e t y l a t e d at room temperature f o r  .18 hours with a c e t i c anhydride I s o l a t i o n of the product from ether-petroleum r ~i22 o LPdjj  + 40  (c, 2.0  of the product was  ( l ml) and p y r i d i n e ( l m l ) .  gave a syrup which c r y s t a l l i s e d  ether (b.p. 3 0 - 6 0 ° ) ' m.p. i n chloroform).  The  R e a c t i o n of 3 , 4 - D I - O - a c e t y l - D - x y l a l  deuterium  tri-O-acetyl  (45). w i t h Carbon  Deuterium  3,4-Di-O-acetyl-D-xylal (8 ml) was  80-82°>  i n f r a r e d spectrum  I d e n t i c a l with that of the  d e r i v a t i v e of the l e v o r o t a t o r y L-lsomer  Monoxide and  debenzoylation  (1.8  g) i n anhydrous benzene  r e a c t e d with carbon monoxide (.1000 p s i ) and (800 p s i ) at 130°  of d i c o b a l t o c t a c a r b o n y l  f o r 3 ^/g hours i n the  (0.4  g).  A f t e r cooling overnight,  unreacted gases were vented, and c a t a l y s t was f i l t r a t i o n through  removed by  a short column of F l o r i s i l as d e s c r i b e d  p r e v i o u s l y , to a f f o r d a syrupi, (1.8 s o l v e n t under reduced product was  presence  pressure.  g) on removal of e l u t i n g A portion (0.8  d e a e e t y l a t e d with methanolic  g) of the  sodium methoxide  - 162 and on working up i n the u s u a l way a syrup (O.56 g) was i s o l a t e d whose I n f r a r e d spectrum showed the presence o f deuterium (C-D s t r e t c h i n g i n 2200-2300 c m  - 1  region).  Paper chromatography showed 2 main components  of s i m i l a r  m o b i l i t i e s t o (44) and ( 4 5 ) , chromatographed a l o n g s i d e as controls.  F r a c t i o n a t i o n of a portion  ( 0 . 4 8 g) of the mix-  t u r e o f deuterated h e x i t o l s by paper chromatography gave the two components, which were s e p a r a t e l y p u r i f i e d by f u r t h e r chromatography on paper.  The two pure f r a c t i o n s were sub-  j e c t e d t o n.m.r. a n a l y s i s as d e s c r i b e d below.  2 1,5-Anhydro-4-deoxy-D-arabino-hexito1-4,6,6-H3 R_ 0 . 4 6 ; r  signals  M S  - 1 1 ° ( c , 3-1 i n w a t e r ) .  3  (83)  N.m.r.  JJ  (D 0): g  multiplet.3.3  - 4 . 0 ? ( 5 ) ; unresolved  c e n t e r e d at 1.53 ppm ( l ) , C-CBH-C.  signal  On removal o f c o u p l i n g  between hydrogen and deuterium the l a t t e r one proton s i g n a l showed as an unresolved  triplet.  1,5- Anhyojr o - 4 - d e o x y - L - x y l o - h e x i t o l - 4 , 6 , 6 - H  R  p  0.40;  [°dp  3  -^5° ( c , 2.4 i n w a t e r ) .  (DgO); m u l t i p l e t 3 . 0 - 4.15  signals  2  c e n t e r e d at I . 9 6 ppm ( l ) , C-CBH-C.  ( c i s ) (84)  N.m.r.  (5)J unresolved  signal  On removal of c o u p l i n g  between hydrogen. and d e u t e r i u m t h e . l a t t e r one proton 1  s i g n a l was r e s o l v e d i n t o a q u a r t e t whose spacing was -  c o n s i s t e n t w i t h a p a i r o f l i n e s separated by 5 . 1 c/s which  - 163 were each s p l i t  -  i n t o two f u r t h e r  l i n e s 2 . 3 c/s a p a r t .  2 , 3 , 6 - T r i -0 -a c e t y l -1,5 -anhyd.ro -4 -deoxy-L-xylo 2 h e x i t o l - 4 , 6 , 6 - H (els) 3  The deuterated anhydrodeoxyhexitol acetylated (l.ml).  with a c e t i c anhydride  (37 mg) was  ( l ml) and anhydrous  pyridine  The product was i s o l a t e d i n the u s u a l way and  c r y s t a l l i s e d from ether-petroleum 82°l  (84)  MS**  -43°  (c, 1.3  ether (b.p. 3 0 - 6 0 ° ) ,  i n chloroform).  m.p.  - 164  -  Experimental S e c t i o n B 3,4,6-Tri-0-acetyl-D-galactal  (a)  (55  D-galactose  g) was  (40)  45  added p o r t i o n w i s e over  minutes, with c o n t r o l of temperature  between 3 5 - 4 0 ° , to a  s t i r r e d s o l u t i o n of a c e t i c anhydride  (200 ml) c o n t a i n i n g  70$ p e r c h l o r i c a c i d  (1.2  ml), and the s o l u t i o n was  overnight at room temperature, Red  phosphorus (15  g) was  or at 40°  stood  f o r 2 hours.  added to the s t i r r e d . s o l u t i o n ,  f o l l o w e d by the dropwlse a d d i t i o n of bromine (29 ml) then of water (15  ml), the temperature  out at or below 20° mixture was  being kept  and  through-  by c o o l i n g i n an ice-water bath.  then warmed to room temperature  and  The  allowed  to stand f o r 3 hours, then f i l t e r e d w i t h s u c t i o n , the r e sidue being washed with a l i t t l e g l a c i a l a c e t i c a c i d .  The  amber c o l o u r e d s o l u t i o n c o n t a i n i n g 2 , 3 , 4 , 6 - t e t r a - 0 - a c e t y l oc-D-galactopyranosyl bromide was  Immediately added  drop-  wise to a z i n c - a c e t i c a c i d r e d u c t i o n mixture c o n t a i n i n g sodium a c e t a t e and copper  s u l p h a t e , maintained  at -5  to  -10  prepared as d e s c r i b e d under 3 , 4 - d i - O - a c e t y l - D - x y l a l ; subsequent  r e a c t i o n and i s o l a t i o n of crude 3 , 4 , 6 - t r i - O - a c e t y l -  D - g a l a e t a l was  a l s o c a r r i e d out as d e s c r i b e d f o r the  t i o n of the p e n t a l .  The  crude product was  t i o n a l d i s t i l l a t i o n under h i g h vacuum. 1 3 5 - 1 3 9 ° / 0 . 5 mm  The  isola-  p u r i f i e d by f r a c fraction  b.p.  (46 g) c r y s t a l l i s e d s l o w l y on standing i n  - 165 the r e f r i g e r a t o r ; [cx]^ 1 . 4 6 7 1 ; one  2  -15°  (e, 7.0  zone by T.L.C. (benzene-methanol, 96:4  (89)  was  added to the hydrobromination  s t a n d i n g at room temperature  bromide  (150  Chloroform  ml)  r e a c t i o n mixture  f o r 2 hours, and the  after mixture  f i l t e r e d through a l a y e r of g l a s s wool, the r e a c t i o n  f l a s k and f i l t e r f u n n e l being washed w i t h an  additional  30 ml of chloroform, and v i g o r o u s l y e x t r a c t e d w i t h (400 ml and 150  portions  form l a y e r was of  0  i s o l a t e d d u r i n g the p r e p a r a t i o n of 3 , 4 , 6 - t r i - O -  a c e t y l - D - g a l a c t a l on one o c c a s i o n .  was  n^  v/v).  2,3*4,6-Tetra-0-acetyl-cx-D-galactopyranosyl  (b)  was  i n chloroform) 3  ml) of i c e - c o l d water.  two  The c h l o r o -  added to a s t i r r e d s a t u r a t e d aqueous s o l u t i o n  sodium hydrogen carbonate  in a 1 I  beaker,  and the mix-  t u r e was  t r a n s f e r r e d to 'a s e p a r a t o r y f u n n e l and  shaken.  The  separated c h l o r o f o r m l a y e r was  minutes with dry s i l i c i c  acid  thoroughly 10  stirred.for  (5 g ) , f i l t e r e d and  under reduced pressure to a p a l e yellow syrup.  evaporated  This  was  d i s s o l v e d i n e t h e r (300 ml) and shaken w i t h c h a r c o a l (5 g ) , calcium chloride g),  ( 5 g) and sodium hydrogen carbonate  f i l t e r e d , and the s o l v e n t removed under reduced  u n t i l about 75 ml of ether remained. r e f r i g e r a t o r the product  m.p.  82-83°.  pressure  On standing i n the  c r y s t a l l i z e d , and was  from ether-petroleum e t h e r (b.p. 3 0 - 6 0 ° ) .  (89),  (0.5  r e c r y s t a l l i s ed  Y i e l d 89 g of  - 166 _ In  cases where attempted  d i s t i l l a t i o n o f crude  3*4,6-  t r i - O - a c e t y l - D - g a l a c t a l under reduced pressure r e s u l t e d i n decomposition,  p u r i f i c a t i o n was e f f e c t e d by chromatography  on a column o f P l o r i s i l , prewashed w i t h anhydrous benzene, using benzene-methanol (10G'2, v/v) as developing s o l v e n t . The  f i r s t zone to be e l u t e d (one spot by T.L.C.) was  i d e n t i f i e d as 3 * 4 , 6 - t r i - 0 - a c e t y l - D - g a . l a c t a l by comparison of  i t s i n f r a r e d and n.m.r. s p e c t r a w i t h those of an a u t h e n t i c  sample. R e a c t i o n o f 3 , 4 , 6 - T r i - O - a c e t y l - D - g a l a c t a l w i t h Carbon Monoxide and Hydrogen R e a c t i o n c o n d i t i o n s and product  isolation  procedures  were i n g e n e r a l s i m i l a r t o those employed p r e v i o u s l y w i t h 3,4-di-O-acetyl-D-xylal. D-galactal  A s o l u t i o n of 3 , 4 , 6 - t r i - O - a c e t y l -  (15 g) and d i c o b a l t o c t a c a r b o n y l ( 3 . 5 g) i n an-  hydrous benzene (50 ml) was shaken w i t h carbon monoxide (1300  p s i ) and hydrogen (1900 p s i ) i n a h i g h p r e s s u r e r e -  a c t i o n v e s s e l at 1 3 O - I 3 5 room temperature  0  f o r 2 I / 2 hours.  the decrease  On c o o l i n g t o  i n pressure was approximately  e q u i v a l e n t to the a b s o r p t i o n of 3 moles of gas (C0+2Hg). A f t e r p r e s s u r e was r e l e a s e d , the r e a c t i o n mixture was t r a n s f e r r e d t o a column (14 x 8 cm diam.) o f F l o r i s i l and c a t a l y s t was e l u t e d with petroleum w i t h benzene-ethanol  ether (b.p. 3 0 - 6 0 ° ) .  Elution  ( 9 1 * v/v) and e v a p o r a t i o n of s o l v e n t  gave a syrup ,(.13.5 g) •  :  - 167 Beacetylation at room temperature  -  w i t h 0.1N  sodium methoxide i n methanol  f o r 18 hours, n e u t r a l i s a t i o n w i t h s o l i d  carbon d i o x i d e and e v a p o r a t i o n of s o l v e n t  gave a water-  s o l u b l e product which, a f t e r d e i o n i s a t i o n w i t h Amberlite IR-120 (H ) r e s i n and f r e e z e - d r y i n g , +  afforded  a partially  c r y s t a l l i n e product c o n s i s t i n g p r i n c i p a l l y of a mixture of two p o l y o l s i n approximately equal amounts. the two main components of the mixture was preparative  I s o l a t i o n of c a r r i e d out by  paper chromatography to g i v e F r a c t i o n A (Rp  and F r a c t i o n B (R„ 0 . 2 1 ) . mixture, 0.16  From an amount of 0.43  g of A and 0.14  Characterisation  0.24)  g of crude  g of B were i s o l a t e d .  of F r a c t i o n s  A and B  F r a c t i o n A (2,6-anhydro-3-deoxy-B-galacto-heptitol F r a c t i o n A, Rp 0.24, was c l a r i f i e d and d e c o l o u r i s e d of C e l i t e - D a r c o  60,  d i s s o l v e d i n methanol,  by f i l t r a t i o n through a l a y e r  and c r y s t a l l i s e d by the a d d i t i o n of  i s o p r o p y l ether to t u r b i d i t y ; m.p. (c, 0 . 8  i n water).  Found *  C, 4 7 . 5 0 ; H, 8 . 0 7 . ,  1  3.25  - 4'. 13  (8);  (91))  C a l c . f o r C^H.^0^  c,  N.m.r. s i g n a l s  m u l t i p l e t 1.32  M p  158-159°'  - 1.87  ppm  7  + 2 4 °  4 7 . 1 8 , H, (BgO) : (2).  7.92.  multiplet  - 168 2,6-Anhydro-3-deoxy-l,4,5,7-tetra-O-p-nitrobenzoylD-galacto-heptitol  F r a c t i o n A (35 mg) was heated w i t h p - n i t r o b e n z o y l ( 0 . 3 0 g) i n anhydrous p y r i d i n e  chloride  f o r 1 hour.  ( 1 . 5 tnl) a t 90°  I s o l a t i o n of the..product i n the u s u a l way gave  (95 mg) which was r e c r y s t a l l l s e d  a sclid  petroleum  from e t h y l a c e t a t e -  Mjj  ether (b.p. 30-60°); m.p. 2 1 0 - 2 1 1 ° :  (c, 2 . 0 i n c h l o r o f o r m ) . H, 3 . 3 8 ; N, 7 . 2 3 .  Found:  C a l c . f o r C^H^O-j^H^:  3  -12°  C, 5 4 . 2 8 ;  C, 54.6.1; H, 3-5©; N, 7 . 4 7 -  F r a c t i o n B ( 2 6 - a n h y d r o - 3 - d e o x y - D - t a l o - h e p t i t o l (90)) J  The slower-moving  component, R  p  0 . 2 1 , was c r y s t a l l i s e d  i n a s i m i l a r way from m e t h a n o l - i s o p r o p y l e t h e r ; m.p. l68°#  LP3  +68° ( c , 1.1 i n w a t e r ) .  D  4 7 . 1 8 ; H, 7 . 9 2 . (D 0):  Found:  C a l c . f o r C^H^O^:  C, 4 6 . 9 4 ; H , 8 . 2 2 .  C,  N.m.r. s i g n a l s  m u l t i p l e t 3 . 3 6 - 4 . 3 3 ( 8 ) ; m u l t i p l e t 1.53 - 2.13  2  ppm ( 2 ) . 2,6-Anhydro-3-deoxy-l,4,5,7-tetra-0-p-nitrobenzoylD-talo-heptitol  A p o r t i o n of the c r y s t a l l i n e F r a c t i o n B was converted t o a t e t r a - 0 - p - n i t r o b e n z o y l d e r i v a t i v e i n the u s u a l way t o g i v e a s o l i d which was r e c r y s t a l l i s e d from c h l o r o f o r m petroleum ether (b.p. 3 O - 6 0 ) ; m.p. 1 2 9 - 1 3 0 ° ( s o f t e n i n g a t 0  -  J  1 1 3 - 1 1 5 ° ) C  3 5  H,  H  2 6 ° 1 7  3.45J  [pc]  4  N  :  G  (c,  +23  >  169  H,  5 4 . 2 8 ;  0.8  -  i n chloroform).  3-38; N,  Cale. for  Found:  7.23.  C,  54.595  7.70.  N,  2,6-Anhydro-3-deoxy-4,5-O-isopropylidene-D-talo-  1  1  1  1  1  1  1  1  1  1  ,  I  I  heptitol ( 1 0 0 ) F r a c t i o n B ( 5 5 wig) i n anhydrous t a i n i n g 4 $ s u l p h u r i c a c i d was  acetone  (2 ml)  con-  s t i r r e d at room temperature  f o r 20 hours w i t h e x c l u s i o n o f m o i s t u r e .  Neutralisation  w i t h 5N sodium hydroxide s o l u t i o n , f i l t r a t i o n to remove sodium  s u l p h a t e and e v a p o r a t i o n gave an o i l .  T h i s was  ex-  h a u s t i v e l y e x t r a c t e d w i t h b o i l i n g carbon t e t r a c h l o r i d e , which on e v a p o r a t i o n under reduced p r e s s u r e gave a c r y s t a l l i n e r e s i d u e of the mono-isopropylidene d e r i v a t i v e  (100)  (23 mg).  residue  F u r t h e r treatment of the CClf|- i n s o l u b l e  w i t h a c i d i f i e d acetone as d e s c r i b e d above a f f o r d e d an a d d i t i o n a l amount  (21 mg)  of the d e r i v a t i v e .  products were r e c r y s t a l l i s o d from carbon m.p. for C 7.97.  104-105°; 1 0  H  l  8  0  :  [ocjg +12° 1  C,  5 5 . 0 3 ;  The  combined  tetrachloride;  (c, .1.6 In c h l o r o f o r m ) . H,  8.31.  Found:  C,  Calc.  54.82;  H,  - 170 2 6-Anhydro-3-deoxy-4,5-O-isopropylidene-1,7-di-01  ( p - t o l y l s u l p h o n y l ) - D - t a l o - h e p t l t o l (106) To a s o l u t i o n o f the mono-lsopropylidene d e r i v a t i v e (100)  (33 mg) i n d r y p y r i d i n e  sulphonyl chloride  (66 mg).  ( 1 . 0 ml) was added p-tolueneA f t e r standing f o r 18 hours  at room temperature i n a stoppered f l a s k the s o l u t i o n was s t i r r e d w i t h water  ( 0 . 1 ml) f o r 20 minutes.  More water  was added u n t i l the s o l u t i o n became t u r b i d , and on standing crystals  (50 mg) o f the d l - O - p - t o l y l s u l p h o n y l d e r i v a t i v e  formed.  The product was r e c r y s t a l l i s o d from methanol;  m.p. 1 3 5 ° ;  Mp  C 4H" 0 S :  C, 5 ^ . 7 8 ; H, 5 - 7 4 .  2  30  9  2  3  -42° (c, 1.7  i n chloroform).  Calc. f o r  C, 5 5 . 0 8 ; H, 6 . 0 1 .  Found:  R e a c t i o n o f (106) w i t h Sodium I o d i d e (a)  When a s o l u t i o n o f the d i - O - p - t o l y l s u l p h o n y l  vative  (106) (8.4 mg) and sodium i o d i d e  deri-  (25 mg) i n acetone  (0.4 ml) was heated i n a s e a l e d tube a t 1 1 8 ° f o r 26 hours, sodium p-toluenesulphonate was p r e c i p i t a t e d i n an amount (6.4  mg) e q u i v a l e n t t o the replacement of both t o s y l o x y  groups o f (106) by i o d i d e . (b)  When the s e a l e d tube r e a c t i o n  ( 8 . 0 mg o f (106) i n  acetone ( 0 . 5 ml) c o n t a i n i n g sodium i o d i d e  (23 mg)) was  c a r r i e d out at 1 0 0 ° , an a p p r e c i a b l e q u a n t i t y of sodium pt o l u e n e s u l p h o n a t e was p r e c i p i t a t e d w i t h i n minutes. 25 minutes the amount i s o l a t e d  After  ( 2 . 8 mg) was approximately  - 171  -  e q u i v a l e n t to the replacement of only one  of  t o s y l o x y group  (106). Consumption of Periodate  Ion  Fraction A Absorbance readings at 223 tervals  tflyw were measured at i n -  1 cm c e l l s ) of an aqueous s o l u t i o n  (Beckmann DU,  c o n t a i n i n g 0.457 x 10 M of F r a c t i o n A and _2t  of sodium p e r i o d a t e  (Reading  A).  0.917  Simultaneous  x  10"V  readings  4 were taken of a s o l u t i o n c o n t a i n i n g 0.457 x 10 t i o n A (B)i  and of a s o l u t i o n c o n t a i n i n g 0.917  sodium p e r i o d a t e  M of F r a c x 10~^M  of  (C). (B+C)-A( ) b  (B C)-A( )  Time  a  +  C  o  Moles p e r i o d a t e / •mole s u b s t r a t e  1  min  0.289  0.312  O.63  47  min  0.448  0.483  0.97  17  hours  0.401  0.433  0.87  (a) :  decrease i n absorbance due periodate  to consumption of  (b) :  f r a c t i o n of known amount of p e r i o d a t e consumed  Fraction B By a s i m i l a r procedure, corresponding  but at a 1 5 - f o l d  dilution,  values obtained w i t h F r a c t i o n B were  - 172  Time (hrs)  -  (B+C)-A  (B+C)-A  Moles p e r i o d a t e / mole s u b s t r a t e  o  C  1  0.463  0.473  0.88  2  0.477  .0.487  0.91  9  0.478  0.490  0.92  23  0.503  O.51.I  0.95  2-Deoxy-3-0-(l,3-dlhydroxy-2-propyl)-  Enantiomeric  (94)  glycero-tetritols  F r a c t i o n A (53 mg)  (95)  and  was  (80 mg,  ml) c o n t a i n i n g p e r i o d i c a c i d course of the o x i d a t i o n was  dissolved  i n a solution  5©$ e x c e s s ) , and  (5 the  f o l l o w e d by o b s e r v i n g the  change i n o p t i c a l r o t a t i o n of the s o l u t i o n , c o n t a i n e d i n a 2 dm p o l a r i m e t e r tube p r o t e c t e d from l i g h t .  After 2  hours the s o l u t i o n was  carbonate  n e u t r a l i s e d w i t h barium  and f i l t e r e d i n t o a s o l u t i o n of sodium borohydride mg)  i n water (3 m l ) .  the s o l u t i o n was  A f t e r 90 minutes at room  +  to a s o l i d , which was  resin, filtered  (52  methanol to a f f o r d a syrup N.m.r. s i g n a l s  sharp s i g n a l at 3.68  1.47  - 1.92  ppm  (2).  (D o):  (l0)j  2  and  r e p e a t e d l y evaporated  r water).  temperature  neutralised with acetic acid, deionised  by s t i r r i n g w i t h Amberlite IR-120 (H ) evaporated  (5©  mg);  multiplet  -125  L°y  multiplet  with  D  +21° 3.50  (apparent  (c, 3.7 - 3.85,  in with  quartet)  -  173  -  The d e x t r o r o t a t o r y t e t r o l ether was c h a r a c t e r i s e d derivative; a portion ( 2 1  as the t e t r a - O - p - n i t r o b e n z o y l  mg) was heated with p - n i t r o b e n z o y l c h l o r i d e ( 0 . 2 g) i n pyridine  ( l ml) and the product  manner as a syrup  was i s o l a t e d i n the u s u a l  ( 8 5 mg) which s o l i d i f i e d s l o w l y on stand-  i n g under methanol a t room temperature, and was r e c r y s t a l l i s e d r -i24 o , , . from e t h y l a c e t a t e ; m.p. 1 5 0 - 1 5 1 ; LP<] +23 (c, 0 . 9 i n n 0  D  chloroform). N,  Calc. f o r  Found:  7 . 2 1 .  C,  C35H28O17N4  54.46;  H,  c,  !  N,  3-55J  5 4 . 1 3 ;  H,  7 . 2 9 .  F r a c t i o n B ( 4 9 mg) was s i m i l a r l y converted date o x i d a t i o n f o l l o w e d by sodium borohydride w i t h i s o l a t i o n o f the product  i n water),  by p e r i o -  reduction,  as d e s c r i b e d above, t o a  ( 4 9 mg);  l e v o r o t a t o r y t e t r o l ether  3 . 6 3 ;  [p<]|p - 2 3 ° ( c , 3 . 2  whose n.m.r. spectrum.(D^O) was i d e n t i c a l  with  that d e s c r i b e d above f o r the d e x t r o r o t a t o r y enantiomer. A p o r t i o n ( 2 1 mg) o f the product  was converted  i n the u s u a l  manner t o a t e t r a - O - p - n i t r o b e n z o y l d e r i v a t i v e which was c r y s t a l l i z e d as d e s c r i b e d above; m.p. (c, H,  1.1 3 . 6 3 .  i n chloroform). Founds  C,  1 5 0 - 1 5 1  0  ;  - 2 3 °  C a l c . f o r C^HggO-jjNjj *• ' C,  5 4 . 5 5 ;  H,  3 . 7 1 .  of the two t e t r a - p - n i t r o b e n z o a t e s were  The i n f r a r e d identical.  54.13J  spectra  - 174  -  Attempted Syntheses o f O p t i c a l l y Pure T e t r o l Ethers (a)  (95)  Attempted S y n t h e s i s of L-Isomer  2,5-Anhydro-  from  —  D-glucose (117)  :  -  '"<"•'  • • r o '  D-Arabino-tei;raacetpxy-l-nltro-l-hexene  (12$  To a suspension of D-arabinose (25 g) i n anhydrous (50 ml) and anhydrous nitromethane (90 ml) i n a  methanol  500 ml, 3-necked f l a s k f i t t e d w i t h an e f f i c i e n t mechanical s t i r r e r was added a s o l u t i o n of sodium (5*25 g) In anhydrous methanol (175  ml).  The mixture was  s t i r r e d at room tempera-  t u r e f o r 20 hours .with e x c l u s i o n of m o i s t u r e , and the r e s u l t i n g s o l i d mass of sodium a c l - n l t r o a l c o h o l s was  collected  by f i l t r a t i o n and washed w i t h a s m a l l volume o f c o l d methan o l and with petroleum ether sidue was  (b.p. 3 0 - 6 0 ° ) .  The s o l i d r e -  immediately d i s s o l v e d i n i c e - c o l d water (200 ml)  and d e i o n i s e d by passage through a column c o n t a i n i n g Dowex50 t"H ) r e s i n +  (200 m l ) .  The e f f l u e n t and washings  (total  500 ml) were c o n c e n t r a t e d under reduced p r e s s u r e to a brown syrup, which was twice evaporated to dryness w i t h a b s o l u t e ethanol.  On standing over PgO^  t n  e  r e s i d u e S o l i d i f i e d to  a c r y s t a l l i n e mass which was washed w i t h c o l d e t h a n o l t o (119)  g i v e a mixture of n i t r o a l c o h o l s film):  1550  cm"  1  ( s ) , 1365  cm"  1  (m)  (16.5 (NOg  g).  I.R.  stretching).  (liquid  - 175 The mixture  (l6.5  of n i t r o a l c o h o l s  i n a c e t i c anhydride  (200  ml) c o n t a i n i n g 2 drops of concentrated heated f o r 1 hour on a  s u l p h u r i c a c i d , and the s o l u t i o n was steam bath.  g) was d i s s o l v e d  I s o l a t i o n of the product i n the u s u a l way  (120).  a syrupy mixture of a c e t y l a t e d n i t r o a l c o h o l s (liquid film):  1565  The product was  d i s s o l v e d i n benzene (600  cm"  1  ( s ) , 1375  cm"  (s) (N0  1  gave I.R.  stretching).  2  m l ) , sodium hydrogen  carbonate  (50  2 hours.  F i l t r a t i o n of the c o o l e d mixture and removal of  g) was  added and the mixture was  s o l v e n t under reduced mass.  pressure gave a p a l e y e l l o w  crystalline  R e c r y s t a l l J s a t i o n from e t h a n o l gave D - a r a b i n o - t e t r a -  acetoxy-l-nitro-l-hexene I.R.  refluxed for  (Nujol):  jugation with  1510  cm"  1  (121), (16.5 (m), 1350  cm"  g)J m.p. 1  (m)  113-115°.  (NOg  i n con-  C=C).  2-Acetamido-l,2-dideoxy-l-nitro-D-mannitol  (122)  To D - a r a b l n o - t e t r a a c e t o x y - l - n l t r o - l - h e x e n e (15 i n a 500  ml f i l t e r f l a s k was  mixture was  added methanol (150  ml); the  c o o l e d i n i c e and s a t u r a t e d w i t h anhydrous  ammonia, when the n i t r o o l e f i n d i s s o l v e d . to room temperature  A f t e r warming  over 8 hours with p r o t e c t i o n from moi-  s t u r e , the s o l v e n t was gen.  g)  The r e s i d u e was  evaporated  i n a stream of dry n i t r o -  f i l t e r e d w i t h the a i d of c o l d a b s o l u t e  e t h a n o l and r e c r y s t a l l l s e d from e t h a n o l to a f f o r d acetamido-l,2-dideoxy-l-nitro-D-mannitol  (122)  (4.4  2g);  - 176 m.p.  171-172°.  A mixture  o f (122)  and I t s epimer  (123)  was o b t a i n e d from the mother l i q u o r s . 2-Amino-2-deoxy-D-mannose h y d r o c h l o r i d e ( l l 6 ) A s o l u t i o n o f (122) solution  ( 4 . 4 g) i n 2N sodium hydroxide  (10 ml) was added dropwlse a t room temperature  concentrated h y d r o c h l o r i c a c i d  (9 ml) w i t h v i g o r o u s  The r e s u l t i n g s o l u t i o n was brought  briefly  to  stirring.  to b o i l i n g point,  c o o l e d t o 0 ° , s a t u r a t e d with hydrogen c h l o r i d e , and f i l t e r e d to  remove sodium c h l o r i d e .  A f t e r d i l u t i o n w i t h water  (10  ml) the s o l u t i o n was f i l t e r e d through a l a y e r of C e l i t e Darco 60 and c o n c e n t r a t e d under reduced pressure t o a syrup, which was stood o v e r n i g h t under vacuum, over to remove r e s i d u a l hydrogen c h l o r i d e .  The product  KOH, was  by d i s s o l v i n g i n methanol (10 ml) c o n t a i n i n g  crystallisfed  2-3 drops of water and adding acetone  to t u r b i d i t y .  S c r a t c h i n g , c o o l i n g and p e r i o d i c a d d i t i o n s of acetone a f f o r d e d 2-amino-2-deoxy-D-mannose h y d r o c h l o r i d e ( 3 . 2 g)  L  —1 pp  "3-5  n  '>  (c, 4.3 i n water).  Attempted P r e p a r a t i o n o f 2,5-Anhydrd-D-glucose  (117)  To a s o l u t i o n o f 2-amino-2-deoxy-D-mannose h y d r o c h l o r i d e (3 g) i n water (50 ml) was added mercuric oxide the mixture was heated The  (16 g) and  on a b o i l i n g water bath f o r 3© minutes.  c o o l e d mixture was f i l t e r e d ,  s a t u r a t e d w i t h hydrogen  - 177'  -  s u l p h i d e , r e f i l t e r e d through G e l i t e - c h a r c o a l and  evaporated  under reduced pressure to a syrup.  crystallise  T h i s d i d not  on d i s s o l v i n g i n a s m a l l volume of methanol; c o n s i d e r a b l e darkening of the product ensued on s t a n d i n g and o n l y a brown amorphous s o l i d was (b)  Attempted  obtained.  S y n t h e s i s of D-isomer (94)  D-mannose ( 1 1 5 ) .  from 2,5-Anhydro-  2,5-Anhydro-D-mannose  (115)  A s o l u t i o n of 2-amino-2-deoxy-D-glucose h y d r o c h l o r i d e (15  g) i n water (100  ml) was  c o o l e d i n an i c e - s a l t  bath  u n t i l a q u a n t i t y of i c e had formed i n the s o l u t i o n . t h i s was  added sodium n i t r i t e  water (35  (6.0  To  g) d i s s o l v e d .in i c e - c o l d  ml) c o n t a i n i n g g l a c i a l a c e t i c a c i d  ( l ml). T h e x  r e s u l t i n g s o l u t i o n was,kept near i t s f r e e z i n g p o i n t f o r 2^/2  hours and then stood i n the r e f r i g e r a t o r f o r 24  hours.  Glacial acetic acid  s o l u t i o n was  (1.5  ml) was  added and  v i g o r o u s l y a e r a t e d at room temperature  the for  30 minutes t o remove n i t r o u s a c i d , and then evaporated t o o a mobile syrup under reduced pressure at 25 was  .  dehydrated by s e v e r a l e x t r a c t i o n s w i t h 10-15  The  product  ml p o r t i o n s  o f anhydrous acetone, d i s s o l v e d i n methanol, f i l t e r e d evaporated t o a syrup, which was under reduced p r e s s u r e at 25°  and  twice evaporated t o dryness  w i t h anhydrous benzene.  r e s u l t i n g 2,5-anhydro-D-mannose (10.5 as'ithe p-nitrophenylhydrazone, m.p.  The  g) was c h a r a c t e r i z e d 179-181°.  - 178 ,Attempted  Preparation of Acetylated N i t r o o l e f i n  To a s t i r r e d s o l u t i o n o f 2,5-anhydro-B-mannose i n anhydrous (4Jp  methanol  ml) i n a 250  (30  ml) and anhydrous  (2.5  immediate  f o r m a t i o n o f a white s o l i d .  g) i n anhydrous  room temperature  (70  methanol  nitromethane  ml), with  A f t e r s t i r r i n g at  f o r 3 hours w i t h e x c l u s i o n of moisture  s o l i d was c o l l e c t e d by f i l t r a t i o n and l u s h e d w i t h a  s m a l l volume o f c o l d methanol (b.p. (100  g  ml, 3-necked f l a s k was added a s o l u t i o n  of sodium  the  (10  30-60°).  and with^fpetroleum e t h e r  The s o l i d was d i s s o l v e d  i n ice-cold  water  ml) and d e i o n i s e d by passage through a column.of  Dowex-50  (H ) r e s i n . +  E v a p o r a t i o n o f the combined e f f l u e n t  and washings under reduced p r e s s u r e gave a syrup which was d r i e d by a z e o t r o p i n g w i t h benzene-ethanol.  (7.5  The product  P °5*  g) d i d not c r y s t a l l i s e on s t a n d i n g over  (liquid film):  1550  cm"  1  ( s ) , 1365  cm"  1  I , R >  2  (m) (N0  stretch-  2  i n g ) * T.L.C. ( w a t e r - s a t u r a t e d e t h y l methyl k e t o n e ) ; two closely-moving  zones.  The mixture o f n i t r o - a l c o h o l s i n a c e t i c anhydride (100  (7.5  g) was  dissolved  ml) c o n t a i n i n g 2 drops o f s u l p h u r !  a c i d and the s o l u t i o n was heated on a steam bath f o r 1 hours and stood o v e r n i g h t a t room temperature.  Isolation  of the product i n the u s u a l way gave a syrup (10.0 I.R.  (liquid film):  stretching).  1565  cm"  1  ( s ) , 1375  T h i s was d i s s o l v e d  cm"  1  V2  g);  (s)  i n benzene (200  (N0g.  ml) and  - 179}the s o l u t i o n was  r e f l u x e d w i t h sodium hydrogen carbonate  (20 g) f o r 11 hours.  The I n f r a r e d spectrum of the syrupy  product I s o l a t e d by f i l t r a t i o n and e v a p o r a t i o n of s o l v e n t was  unchanged from that of the mixture of a c e t y l a t e d  alcohols.  No change i n the i n f r a r e d spectrum was  nitro-  observed  on f u r t h e r r e f l u x i n g i n benzene s o l u t i o n w i t h anhydrous sodium a c e t a t e . 2-Deoxy-3-0-(l,3-'dihydroxy-2-propyl) - L - g l y c e r o - t e t r i t o l (95)  from 2,6-Anhydro-3-deoxy-D-gluco-heptltol  (l30)( ) a  O x i d a t i o n of 2 , 6 - a n h y d r o - 3 - d e o x y - D - g l u c o - h e p t i t o l (130)  w i t h an excess of p e r i o d i c a c i d , f o l l o w e d by r e d u c t i o n  of the r e s u l t i n g dialdehyde with an aqueous s o l u t i o n of sodium borohydride i n water, and . i s o l a t i o n of the product as d e s c r i b e d p r e v i o u s l y gave 2 - d e o x y - 3 - 0 - ( l , 3 - d i h y d r o x y - 2 propyl) - L - g l y c e r o - t e t r i t o l  (95);  The t e t r o l e t h e r (95)  water).  benzoyl d e r i v a t i v e , m.p.  [oc]  2  2 )  + 26  0  ( c , 2.9 i n  formed a t e t r a - 0 - p - n i t r o -  151-152°;  [P<D§ +22 1  0  1.2  (c,  i n c h l o r o f o r m ) . The m e l t i n g p o i n t of t h i s d e r i v a t i v e undepressed  was  on admixture w i t h the c o r r e s p o n d i n g d e r i v a t i v e  of the d e x t r o r o t a t o r y t e t r o l e t h e r prepared from F r a c t i o n A, (  + 2 3 ° ) , and the i n f r a r e d spectra of the two  p-  n i t r o b e n z o a t e s were i d e n t i c a l . (a)  The s t r u c t u r e of 2 , 6 - a n h y d r o - 3 - d e o x y - D - g l u e o - h e p t l t o l ( l 3 0 ) had been e s t a b l i s h e d by c o r r e l a t i o n w i t h - 4 , 5 , Y - t r i - 0 - a c e t y l - 2 , 6 anhydro-3-deoxy-l-0-p-bromobenzenesulphonyl-D-gluco7heptitol (129 ) 5 5 whose -structure had been proved by X-ray a n a l y s i s - ^ fi  1  1  1  t  - 180 Experimental S e c t i o n C H y d r o f o r m y l a t l o n of 3 , 4 - d i - O - a c e t y l - D - x y l a l 3,4-Di-O-aeetyl-D-xylal carbonyl  (12.0 g) and d i c o b a l t o c t a -  (3 g) were d i s s o l v e d i n anhydrous benzene; the  volume o f the s o l u t i o n  (60 ml), c o n t a i n e d i n the g l a s s  l i n e r o f a h i g h pressure r e a c t i o n v e s s e l , gave a net v o i d of  200 ml.  A f t e r f l u s h i n g w i t h carbon monoxide, a d d i t i o n a l  carbon monoxide was added t o a p r e s s u r e of 600 p s i , f o l l o w e d by hydrogen (2400 p s i ) J  on e q u i l i b r a t i o n the i n i t i a l gas  pressure was 2930 p s i a t room temperature. then heated w i t h shaking t o a temperature  The bomb was of 1 1 5 ° .  The  p r e s s u r e i n c r e a s e d t o a maximum o f 3730 p s i a f t e r 35 minutes from the attainment then began t o f a l l .  of a constant temperature, and  A f t e r an a d d i t i o n a l 30 minutes the  r e a c t i o n v e s s e l and contents were r a p i d l y c o o l e d t o room temperature  by immersion i n i c e , when the p r e s s u r e had de-  creased by 220 p s i , t o 2710 p s i , e q u i v a l e n t t o the absorpt i o n o f 2 moles o f s y n t h e s i s gas (H + GO). g  Unreacted gas  p r e s s u r e was r e l e a s e d , the r e a c t i o n mixture was t r a n s f e r r e d to  a column o f F l o r i s i l  e t h e r (b.p. 3 0 - 6 0 ° ) .  roleum alcohol syrup (2.5  and c a t a l y s t was e l u t e d w i t h p e t E l u t i o n with  benzene-isopropyl  (9 1* v/v) and removal o f s o l v e n t then gave a J  (10.0 g).  An a d d i t i o n a l q u a n t i t y o f a mobile  g) was subsequently r e c o v e r e d by f i l t r a t i o n and  syrup  - 181 evaporation: of the petroleum  e t h e r f r a c t i o n , a f t e r decomposi-  t i o n of c a t a l y s t on s t a n d i n g at room temperature. f r a c t i o n , i d e n t i f i e d as 3 , 4 - d i - O - a c e t y l - D - x y l a l trum and T.L.G. (benzene-methanol, 9 6 * 4 , v/v)  The  (I.R.  latter spec-  alongside  an  a u t h e n t i c specimen) c r y s t a l l i s e d on standing i n the r e frigerator. T.L.C. of the main f r a c t i o n  :  a l o n g s i d e 3 , 4 - d i - O - a c e t y l - D - x y l a l and the mixture  v/v)  di-O-acetyl-anhydrodeoxy-hexitols the hydroxymethylation zones corresponding a p o r t i o n (1.5  of ( 2 2 ) ,  p r e v i o u s l y obtained showed two  to both c o n t r o l s .  well  g) of the main f r a c t i o n on a column of  s o l v e n t , gave 3 , 4 - d i - O - a c e t y l - D - x y l a l  and a mixture  of r e a c t i o n products  f r a c t i o n showed a n.m.r. s i g n a l (CHO)  by  Chromatography of  :  developing  of  separated  n e u t r a l alumina, u s i n g benzene-methanol ( 9 5 5 , v/v)  8  95 5.  (benzene-methanol,  (0.93  (CCl^) at  g). &  as  (0.55  g)  The  latter  = 9«35  ppm  ( i n t e n s i t y r e l a t i v e to a c e t a t e a b s o r p t i o n around  = 2 ppm  c o n s i s t e n t w i t h approximately  deoxyanhydro-aldehydo-hexoses (133)  and  A p o r t i o n (1.2  (134)).  g) of the r e a c t i o n mixture  from F l o r i s i l w i t h benzene-iso.propyl (20 ml)  di-O-acetyl-  2,4-Dinitropheny.lhydrazine  R e a c t i o n with  i n ethanol  15$  c o n t a i n i n g 2-3  and the s o l u t i o n was  heated  a l c o h o l was  drops of a c e t i c  eluted dissolved acid,  to b o i l i n g p o i n t on a steam  - 1821bath.  To t h i s was added p o r t l o n w i s e a hot, s a t u r a t e d  s o l u t i o n of 2,4-dinitrophenylhydrazine'in. ethanol, u n t i l the orange c o l o u r Imparted to the s o l u t i o n no l o n g e r to y e l l o w .  On d i l u t i n g w i t h water t o t u r b i d i t y , and standing  i n the r e f r i g e r a t o r , a yellow s o l i d which was c o l l e c t e d by f i l t r a t i o n  (0.39 g) separated,  and d r i e d over  calcium  T.L.C. (benzene-methanol, 95 5* v / v ) ; 2 c l o s e l y  chloride.  :  moving components, F r a c t i o n X (faster-moving) Y (slower-moving),  and F r a c t i o n  plus t r a c e s of o t h e r s ; no a d d i t i o n a l  zones r e v e a l e d with s u l p h u r i c - n i t r i c a c i d spray N.m.r. s i g n a l s  (CDCl^):  reagent.  s i n g l e t 11.07 ( l ) , N-NH-; doublet  (J = 3 c/s) 9.04 ( l ) , aromatic  H^J quartet 8.30 ( l ) ,  aromatic RV; p a i r of o v e r l a p p i n g doublets 7.87  and 7 . 9 5 ( l ) , aromatic  (1),  N CH-; m u l t i p l e t  2.07,  faded  Hg; doublet  ( J = 9 C$te),  (J = 6 cjfs) 7 . 5 8  3 . 1 5 - 5 . 3 5 (5)5 3 sharp s i g n a l s , at  2.12 and 2 . l 6 ppm ( 6 ) , OCOCH^, superimposed on  multiplet  ( 2 ) , C-CH -C. 2  Fraction Y (4,5-Dl-0-acetyl-2,6-anhydro-3-deoxyaldehydo-D-lyxo-hexose  When t h e mixture  2,4-dinitrophenylhydrazone)  of d e r i v a t i v e s  from the r e a c t i o n  with 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e was t r i t u r a t e d with warm ethanol  ( 2 - 3 ml), p a r t i a l d i s s o l u t i o n occurred and a  g r a n u l a r yellow s o l i d separated. filtration,  washed with a l i t t l e  T h i s was i s o l a t e d by c o l d e t h a n o l , and  - 183 r e c r y s t a l l i z e d as f i n e yellow needles hexane; m.p. 225-226°; One  L°il|  2  from c h l o r o f o r m -  -6©° (e, 2.5 In c h l o r o f o r m ) .  95 5,  spot by T.L.C. (benzene-methanol,  sponding mixture.  v/v) c o r r e -  l  t o slower-moving o f two components present i n N.m.r. ( C D C l ^ ) d i f f e r e d from mixture  Y d e s c r i b e d above i n showing doublet ( l ) , aromatic  of X and  (J = 9 4/&) a t 7.85  C-6 proton, and two sharp s i g n a l s 2.13 and  2.17 ppm (6), OCOCH . 3  H, 4.42; N, 13.66.  Gale, f o r C gH gN jO : 1  Pound:  1  ]  g  C, 4,6.83>  C, 46.60; H, 4.64; N, 13-77.  1,5-Anhydro-4-deoxy-D-arabino-hexitol (44) from F r a c t i o n Y An a d d i t i o n a l amount (0.9 g) o f F r a c t i o n Y was p r e pared by r e a c t i o n o f the main f r a c t i o n from the hydroformyl a t i o n o f (22) (6.8 g) with 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e , and i s o l a t i o n as d e s c r i b e d above.  A p o r t i o n (0.4 g) i n c h l o r o -  form (3 ml) was added t o a mixture distilled  pyruvic acid  bromide i n a c e t i c a c i d o at  40-50  erature.  c o n s i s t i n g of f r e s h l y  (4 ml) and a 10$ s o l u t i o n o f hydrogen (0.2 m l ) .  The s o l u t i o n was heated /  f o r 1 hour and then stood overnight A yellow c r y s t a l l i n e s o l i d  by f i l t r a t i o n ,  a t frDom temp-  (0.2 g) was i s o l a t e d  washed with a s m a l l volume of c o l d  and i d e n t i f i e d as p y r u v i c a c i d (m.p., I.R. spectrum).  chloroform,  2,4-dinitrophenylhydrazone  The f i l t r a t e was e x t r a c t e d w i t h two  10 ml p o r t i o n s o f c h l o r o f o r m , and the e x t r a c t was washed with t h r e e 10 ml p o r t i o n s of s a t u r a t e d sodium hydrogen c a r bonate s o l u t i o n t o remove d i s s o l v e d p y r u v i c a c i d 2 , 4 - d i n i t r o -  - 184 phenylhydrazone, and then w i t h water. magnesium sulphate and f i l t e r i n g , reduced  I.R. and  s o l v e n t was removed under  pressure t o a f f o r d a syrup  quantitative).  N.m.r. (CCl^) :  (liquid film): 1700 cm"  1  A f t e r d r y i n g over  (110ragf.r e c o v e r y not  s i n g l e t a t 9.35 ppm (CHO).  c a r b o n y l bands a t 1740 cm"  (ester)  1  (aldehyde); band a t 3400 cm" (OH). 1  When a p o r t i o n (20 mg) o f the aldehydo-compound was reacted i n ethanol s o l u t i o n with  2,4-dinitrophenylhydrazine  as d e s c r i b e d p r e v i o u s l y , a c r y s t a l l i n e product  separated on  c o o l i n g which was i d e n t i f i e d as F r a c t i o n Y (m.p., T . L . C , n.m.r.). A p o r t i o n (35 mg) of the aldehydo-product  from the  exchange r e a c t i o n w i t h p y r u v i c a c i d was d i s s o l v e d i n methanol  (2 ml) and added dropwise t o a s o l u t i o n o f sodium  hydride  (30 mg) i n water (2 m l ) .  boro-  A f t e r s t a n d i n g overnight  at room temperature t h e s o l u t i o n was n e u t r a l i s e d by t h e a d d i t i o n o f a c e t i c a c i d and d e i o n i s e d by passage a s m a l l column o f Amberllte IR-120 (H ) r e s i n . +  bined e f f l u e n t and washings were evaporated r e s i d u e which was r e p e a t e d l y -evaporated methanol t o a f f o r d a syrup  (8 mg).  through The com-  to a solid  t o dryness  with  One spot on paper  chromatography, a l o r e and when superimposed on 1,5-anhydro4-deoxy-D-arabino-hexitol  (44), two spots when superimposed  on the slower-moving L-xylo-isomer ( 4 5 ) .  - 185 (4,5-Pi-0-acetyl-2,6-anhydro-3-deoxy-aldehydo-  Fraction X D-xylo-hexose  2,4-dinitrophenylhydrazone)  The a l c o h o l - s o l u b l e p o r t i o n of the mixture o f hydra zones remaining a f t e r i s o l a t i o n of F r a c t i o n Y as .described above was  evaporated t o a syrup.  A portion  (45 mg) was a p p l i e d i n  c h l o r o f o r m s o l u t i o n as a narrow s t r e a k near t h e lower edge (20 cm wide x 45 cm long x 0 . 8 mm t h i c k ) of s i l i c a  of a p l a t e  g e l G, and f r a c t i o n a t e d by m u l t i p l e ascending development, u s i n g c h l o r o f o r m as d e v e l o p i n g s o l v e n t , w i t h a i r d r y i n g between s u c c e s s i v e developments.  The faster-moving o f the  two major components was c u t out, e l u t e d w i t h c h l o r o f o r m ethanol ( l l , :  v / v ) , f i l t e r e d and evaporated t o a syrup  t which was c r y s t a l l i s e d from chloroform-hexane m.p. 1 3 2 ° ;  M  D  - 1 6 ° (c, 0 . 4 In c h l o r o f o r m ) .  one aeetoxy s i g n a l at 2 . 0 5 ppm.  46.835 H, 4 . 4 2 .  Found:  as f i n e n e e d l e s j N.m.r. (CDC1 ) : 3  Gale, f o r C^gH^gN^O^:  C,  C, 46.901 H, 4 . 1 0 .  D l -0 -a c e t y l -a nhydrodeoxy -a'ldehydo -hexos es (133) and (134)  (74) (a)  by O x i d a t i o n of D i - O - a c e t y l - a n h y d r o d e o x y h e x i t o l s and (75)  To a p o r t i o n ( 0 . 8 8 g) of the syrupy product from the  hydroxymethylation o f 3 j 4 - d i - 0 - a c e t y l - D - x y l a l ( s e c t i o n A), In anhydrous p y r i d i n e chloride  (5 ml) was added p - t o l u e n e s u l p h o n y l  ( 1 . 0 g ) , and t h e mixture was stood at room  temperature  - 1&6 f o r 20 hours. gave a syrup  ll80  —1  cm"  I s o l a t i o n of the product (1.0  (76)  derivatives  (S=0  g) c o n t a i n i n g the and  (77).  methylsulphoxide  minutes the mixture was removed under reduced  1600  cm  1  ( a r o m a t i c ) ; no  ( l . O g) i n anhydrous d i -  added dropwise to a  p a s s i n g a stream of  at 150°  way  6-0-p-tolysulphonyl  mixture  (20 ml) and sodium hydrogen  through which was maintained  i n the u s u a l  ( l i q u i d f i l m ) ; hands at  The product  (5 ml), was  of dimethylsulphoxide  which was  I.R.  s t r e t c h i n g ) and  hydroxyl absorption.  (3 g)>  -  carbonate  nitrogen,.and After 5  i n an o i l b a t h .  c o o l e d , f i l t e r e d , and s o l v e n t  was  pressure to a f f o r d a brown syrup,  whose i n f r a r e d spectrum was  unchanged from that d e s c r i b e d  above. (b)  To a s o l u t i o n of the hydroxymethylation  comprising (0.37  di-0-acetyl-anhydrodeoxyhexitols  carbodiimide  (1.8  g).  acid  (0.1  ml) and  and  (6 ml), was  g) i n anhydrous dimethylsulphoxide  anhydrous phosphoric  (7*0  product  added  N,N'-dicyclohexyl-  A f t e r standing at room temperature  under anhydrous c o n d i t i o n s f o r 24 hours the mixture f i l t e r e d , and the c r y s t a l l i n e r e s i d u e of urea was  (75)  was  N,N'-dicyelohexyl-  washed with a b s o l u t e e t h a n o l to g i v e a t o t a l volume  ( f i l t r a t e +washings) of 30 ml. s o l u t i o n , heated  To a p o r t i o n (15  on a steam bath, was  ml)  of t h i s  added a hot, s a t u r a t e d  s o l u t i o n of 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e i n e t h a n o l , u n t i l orange c o l o u r p e r s i s t e d on b o i l i n g .  an  D i l u t i o n with water to  - 187  -  t u r b i d i t y and c o o l i n g gave a yellow s o l i d which was by f i l t r a t i o n hydrazones  and d r i e d .  collected  S e p a r a t i o n of 2 , 4 - d i n i t r o p h e n y l -  from c o - p r e c i p i t a t e d N,N'-dicyclohexylurea  was  e f f e c t e d by e x t r a c t i o n of the former w i t h a s m a l l volume of  cold chloroform, f i l t r a t i o n  solid of  (165  mg).  and e v a p o r a t i o n to a yellow  P r e p a r a t i v e s c a l e TLC  the mixture of hydrazones  of a p o r t i o n  a f f o r d e d two  (30  mg)  pure components;  4,5-di-Q-acetyl-2,6-anhydro-3-deoxy-aldehydo-D-lyxo-hexose 2,4-dinitrophenylhydrazone  (17  mg),  m.p.'  2 2 5 - 2 2 6 ° , and  2 , 4 - d i n i t r o p h e n y l h y d r a z o n e of the corresponding isomer,  (9 mg),  'fractions  m.p.  132°,  D-xylo-  both i d e n t i f i e d , w i t h the  two  (Y and X r e s p e c t i v e l y ) d e s c r i b e d p r e v i o u s l y .  • When the same experiment of  the  was  c a r r i e d out w i t h omission  the mixture of a c e t y l a t e d anhydrodeoxyhexitols, no p r e -  c i p i t a t e was  I s o l a t e d f o l l o w i n g d i l u t i o n of the r e a c t i o n  mixture w i t h water.  S i m i l a r l y , a c o n t r o l experiment  which N , N ' - d i c y c l o h e x y l c a r b o d i i m i d e was  in  not present d i d  not r e s u l t i n the i s o l a t i o n of any r e a c t i o n product treatment w i t h 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e .  following  - 188 REFERENCES 1.  H. Akins and G. Krsek, J . Am. Chem. S o c , 70, 383 (1948).  2.  I . Wender, M. O r c h i n and H. H. S t o r c h , J . Am. Chem. Soc. 72,  4842 ( 1 9 5 0 ) .  3.  F , F i s c h e r and H. Tropsch, Brennstoff-Chem.,  4.  D. F. Smith, C. 0. Hawk and P. L. Golden, J . Am. Chem. S o c , 5 2 , 3221 ( 1 9 3 0 ) . 0. Roelen, Ger. Patent 103,362 ( f i l e d 1938)? U.S. Patent 2 , 3 2 7 , 0 6 6 (1943)1 Chem. A b s t r a c t s , 3 8 , 550 ( 1 9 4 4 ) .  5.  _4, 276 (1923).  6.  I . Wender, H. W. Sternberg and M. O r c h i n , " C a t a l y s i s " , V o l . 5 , ed. by P. H. Emmett, New York, Reinhold P u b l i s h i n g C o r p o r a t i o n , 1957, p. 7 3 .  7.  H..W. Sternberg and I . Wender, Proceedings o f I n t e r n a t i o n a l Conference on C o o r d i n a t i o n Chemistry, Chem. Soc. Spec. Publn. No. 1 3 , ( 1 9 3 9 ) , P. 3 b . :  8.  C. W. B i r d , Chem. Rev., 6 2 , 283 ( 1 9 6 2 ) .  9.  H. Adkins and G. Krsek,* J . Am. Chem. S o c , 7 1 ,  3051 ( 1 9 4 9 ) .  10.  J . Halpern, Quart. Rev., 10, 463 (1956).  11.  M. O r c h i n , L. K i r c h and I . G o l d f a r b , J . Am. Chem. S o c , 78,-5450 (1956).  —  12.  A. R. M a r t i n , Chem. and I n d . , 1536  13.  G. N a t t a , R. E r c o l i , S. C a s t e l l a n o and P. H. B a r b l e r l , J . Am. Chem, S o c , 7 6 , .4049 (1954). G. L. Karapinka and M. O r c h i n , J . Org. Chem., 2 6 , 4l87 (1961). = L . K i r c h and M. O r c h i n , J . Am. Chem, S o c , 80, 4428 (1958). =  14. 15.  (1954).  16.  I . Wender, S. M e t l i n , S. Ergun, H. W. Sternberg and H. G r e e n f i e l d , J . Am, Chem, S o c , 7 8 , 5401 (1956) .  17.  R. F. Heck and D. S. Breslow, 4023 (1961).  J , Am. Chem, S o c , 8 3 , =  -189  -  18.  D. S. Breslow and R. F. Heck, Chem. and Ind., 467  19.  T. H. C o f f i e l d , J . Kozlkowski and R. D. C l o s s o n , J . Org. Chem., 2 2 , 598 ( 1 9 5 7 ) .  (i960).  '  :  20.  L. Marko, Proc. Chem. S o c , 67  (1962).  21. 22.  C. L . A l d r l d g e and H. B. Jonassen, Nature, 1 8 8 , 4o4 ( i 9 6 0 ) . C. L. A l d r l d g e and H. B. Jonassen, J . Am. Chem. S o c , 8 5 , 886 ( 1 9 6 3 ) .  =  23.  J . G. Traynham, J . Am. Chem. S o c , 7 8 , 4042  24.  I . Wender, J . Feldman, S. M e t l l n , B. H. Gwynn and M. O r c h i n , J . Am. Chem. S o c , 7 7 , 5760 ( 1 9 5 5 ) . J . Falbe and F. K o r t e , B e r . , 9 7 , 1104 ( 1 9 6 4 ) .  25.  (1956).  26.  I . Wender, R. L e v i n and M. O r c h i n , J . Am. Chem. S o c , 72, 4375 ( 1 9 5 0 ) . : — =  27.  E . I . du Pent de Nemours and Co.. B r i t . Patent Chem. A b s t r a c t s , 4 3 , 4685 ( 1 9 4 9 ) .  28.  C. W. B i r d , R. C. Cookson, J . Hudec and R. 0 . W i l l i a m s , J . Chem. S o c , 410 ( 1 9 6 3 ) .  29.  P. F. B e a l , M. A. Rebenstorf and J . E . P i k e , J . Am. Chem. S o c , 8 1 , 1231 ( 1 9 5 9 ) .  6l4,010J  :  30.  A. L . Nussbaum, T. L . Popper, E . P. O l i v e t o , S. Friedman and I . Wender, J . Am. Chem. S o c , 8 l , 1228 ( 1 9 5 9 ) .  31.  E. F i s c h e r and K. Zach, S i t z . b e r . k g l . p r e u s s . Akad. Wiss., 1 6 , 311 (1913) -"CTIem. A b s t r a c t s , 8, 73 ( 1 9 1 4 ) .  32.  R. K. Ness and H. G. F l e t c h e r , J . Org. Chem., 28, 435 (1963). =  33.  E. F i s c h e r , B e r . , 4 7 , 196  34.  E. F i s c h e r , M. Bergmann and H. S c h o t t e , B e r . , 5 3 , 509 (1920). =  35.  L. D. H a l l and L. F. Johnson, Tetrahedron L e t t e r s , 2 0 , 883 ( 1 9 6 4 ) . — —  36.  M. K a r p l u s , J . Chem. Phys., 3 0 , 11 ( 1 9 5 9 ) .  (1914).  - 190 37.  B. H e l f e r i c h , Advances I n Carbohydrate Chem., 7, 209 ( 1 9 5 2 ) .  38.  38.  D. A. P r i n s and R. W. J e a n l o z , Ann. Rev, Biochem., 17,  67 ( 1 9 4 8 ) . 39.  =  !  W. G. Overend and M. Stacey, Advances i n Carbohydrate Chem.,  45 ( 1 9 5 3 ) .  "  :  :  40..  M. B a r c z a i - M a r t o s and P. Korosky, Nature, 165, 369 ( 1 9 5 0 ) .  41.  R. E. D e r i a z , W. G. Overend, M. Stacey, E. G. Teece and L. F. Wiggins, J . Chem. S o c , 1879 ( 1 9 4 9 ) .  42.  W. G. Overend, P. Shafizadeh and M. Stacey, J . Chem, S o c ,  671 43.  ~  B. M. I s e l i n and T. R e i c h s t e i n , Helv. Chlm, A c t a , 27,  1146, 44.  (1950). 1200 ( 1 9 4 4 ) .  =  ;  B, H e l f e r i c h , E. N. Mulcahy and H. Z i e g l e r , Ber., 87>  233 ( 1 9 5 4 ) .  —  -  45.  B. H e l f e r i c h and M. Gindy, Ber., 8 7 , 1488 ( 1 9 5 4 ) .  46.  L. F. P i e s e r and M. F i s e r , Advanced Organic R e i n h o l d P u b l i s h i n g Corp., New York,  47.  H. S. I s b e l l and W. W. Pigman, J , Research N a t l , Bur. Standards, 2 2 , 397 ( 1 9 3 9 ) . '  48.  W. G. Overend, P. S h a f i z a d e h and M. Stacey, J . Chem. S o c ,  Chemistry, I 9 6 I , p. 310.  992 ( 1 9 5 1 ) .  :  ~  49.  F. B. Cramer, J . F r a n k l i n I n s t . , 2 5 3 , 277 ( 1 9 5 2 ) .  50.  C. K. I n g o l d , S t r u c t u r e and Mechanism i n Organic Chemistry, C o r n e l l U n i v e r s i t y F r e s s , i t h a c a , N.Y., 1953, p. 6 6 9 .  51.  J . Meinwald, Y. C. Meinwald and T. N. Baker, J . Am. Chem.  S o c , 8 5 , 2513 ( 1 9 6 3 ) . 52.  W. J . S e r f o n t e i n , J . H. Jordaan and J . White, Tetrahedron L e t t e r s , l B , 1069 (.1964) .  53.  A. Schonberg  and A. Mustafa, Chem, Rev., 40, l 8 l ( 1 9 4 7 ) .  54. 55.  B. H e l f e r i c h and E. von Gross, Ber., 8 5 , 531 ( 1 9 5 2 ) . R. C. Hockett, A. C. Sapp and S. R. Millman, J . Am. Chem.  S o c , 6 3 , 2051 ( 1 9 4 1 ) .  56.  D. H. R. Barton and R. C. Cookson, Quart. Rev., 1 0 , 44  (1956).  =  57.  J . C h a t t , Chem. Rev., 48_, 15  58.  P. T. Manolopoulos, M. Mednick and N. N. L i c h t i n , Chem. S o c , 8_4_, 2203 (1962) .  59.  P. A. Levene and A. L. Raymond, J . B i o l . Chem., 8 8 , 513  (1951).  (1930). 60.  (1964).  =  R. U. Lemieux and S. L e v i n e , Can. J . Chem., 40, 1926  (1962). 62.  =  R. U. Lemieux and B. F r a s e r - R e i d , Can. J . Chem., 42,  532 61.  J . Am.  '  =  A. R o s e n t h a l . D. Read and C. Cameron, S c i e n c e , 1 2 3 ,  1177 ( 1 9 5 6 ) .  =  63.  A. Rosenthal and D. Read, Can. J . Chem., 3 5 , 788 ( 1 9 5 7 ) .  64.  A. Rosenthal and D. Read, Methods i n Carbohydrate Chemistry, V o l . I I , ed. by K. L. w n i s t l e r and M. L. wolrrom, New York, Academic P r e s s , 1 9 6 3 , p. 4 5 7 .  65.  P. A. Levene and T. M o r i , J . B i o l . Chem., 8 3 , 803 ( 1 9 2 9 ) .  66.  F. Weygand, MethodB i n Carbohydrate Chemistry, V o l . I , ed. by R. L. W n i s t l e r and M. L. Wolfrom, New York, Academic P r e s s , 1962, p. 1 8 2 .  67.  W. G. Overend, F. Shafizadeh and M Stacey, J . Chem. S o c ,  1027 68.  (1950).  —;  A. M. Gakhokidze, Zhur. Obschei Khim., 1 5 , 530 (1945)> Chem. A b s t r a c t s , 40, 4673 (1946). =  •69.  D. W. Read, B.A. T h e s i s , U n i v e r s i t y o f B r i t i s h Columbia,  70.  I . Wender, Ph.D. T h e s i s , U n i v e r s i t y o f P i t t s b u r g h , 1950.  71.  C. T. B i s h o p , Methods Biochem. A n a l . 1 0 , 1 ( 1 9 6 2 ) .  72.  G. Zemplgn, A. Gerecs and I . Hadacsy, Ber., 6 9 , 1827  1954.  (1936). 73.  =  J . B a d d i l e y , J . G. Buchanan, R. E. Handschumacher and. J . F. P r e s c o t t , J . Chem. S o c , 2818 ( 1 9 5 6 ) .  - 192 74.  J . M. B o b b i t , Advances In Carbohydrate  75.  R. D. G u t h r i e , Methods In Carbohydrate Chemistry, V o l . I , e d . b y R. L. W h i s t l e r and M. L. Wolfrom, New York, Academic P r e s s , 1962, p. 4 3 5 .  76.  J . S. Dixon and D. L i p k i n , A n a l , Chem,, 2 6 , 1092 ( 1 9 5 4 ) .  77.  C. E. Crouthamel, H. V. Meek, D. S. M a r t i n and C. V. Banks, J , Am, Chem, S o c , 7 1 , 3031 ( 1 9 4 9 ) .  78,,  Rules o f Carbohydrate  I  281 ( 1 9 6 3 ) .  Chem., 11, .1 ( 1 9 5 6 ) .  Nomenclature, J . Org. Chem., 2 8 ,  =  79.  L . M. Jackman, A p p l i c a t i o n s o f Nuclear Magnetic Resonance Spectroscopy i n Organic Chemistry, Fergamon Press L t d . , London, 1 9 5 9 , p. 5 5 .  80.  E. von R u d l o f f , D. E. S t u e t z and H. F. Bauer, Can, J . Chem,, J 5 , 315 ( 1 9 5 7 ) .  81.  M. L. Wolfrom and A. Thompson, Methods i n Carbohydrate Chemistry, V o l . I I , ed. by R. L. W h i s t l e r and M. L. Wolfram, New York, Academic P r e s s , 1 9 6 3 , p. 6 5 .  82.  P. A. J . G o r l n , Can, J , Chem., 3 8 , 64l ( i 9 6 0 ) .  83.  F. L. Benton and T. E. D i l l o n , J . Am, Chem, S o c , 64,  1128  (1942).  :  s a  "  84.  Our thanks are due to Dr. E. von R u d l o f f , N a t i o n a l Research C o u n c i l P r a i r i e R e g i o n a l L a b o r a t o r y , Saskatoon, Sask., f o r s u p p l y i n g a sample of. t h i s compound.  85.  P. A. J . G o r i n , J . Org. Chem., 2 4 , 49 ( 1 9 5 9 ) .  86.  A. S. P e r l i n , E . von R u d l o f f and A. P. T u l l o c h , Can. J . Chem., J 5 , 1504 ( 1 9 5 7 ) .  87.  A. B. F o s t e r , W. G. Overend. M. Stacey and G. Vaughan, J . Chem, S o c , 3367 ( 1 9 5 4 ) .  88.  F. S h a f i z a d e h , Methods In Carbohydrate Chemistry, V o l . I I , ed. by R. L. W h i s t l e r and M. Wolfrom, New York, Academic P r e s s , 1 9 6 3 , p. 4 0 9 .  89.  F. S h a f i z a d e h and M. Stacey, J . Chem. S o c , 3608 ( 1 9 5 2 ) .  90.  C. Tamm and T. R e i c h s t e i n , H e l v . Chlm. A c t a , 3 1 , 1630 (1948)  - 193  -  91.  A. B. P o s t e r , W. 974 ( 1 9 5 1 ) .  92.  W. N. Haworth, L. N. Owen and P. Smith, J . Chem. S o c , (1941).  93.  P. A. Levene and A. L. Raymond, J . B i o l . Chem., 102, (1933). =  94.  J . W. H. Oldham and J . K. R u t h e r f o r d , J . Am. 54,  366  G. Overend and M. Stacey, J.- Chem. S o c , "  (1932).  ~  S. Peat, Advances i n Carbohydrate Chem., 2 ,  96. 97.  R. C r i e g e e , E. Buchner and W. Walther, Ber., 7 3 , C. S. Hudson, J , Am. Chem. S o c , 3 1 , 66 (1909) .  98.  B. Coxon and H. G. F l e t c h e r , J . Am. (1963). C. W.  Smith  (1949)J  317  Chem. S o c ,  95.  99.  88  38  Chem. S o c ,  3036b  571 85,  (1940). 264l  =  (to S h e l l Development Co.), U.S.  Chem. A b s t r a c t s , 4 4 ,  (1946).  Patent 2 , 4 8 9 , 7 2 9  (1950).  100.  K. Z i e g l e r , Organic Synth.,- C o l . V o l . I , 314  101.  V. M i g r d i c h i a n , The Chemistry o f Organic Cyanogen Compounds, Reinhold P u b l i s h i n g uorp., New York, l 9 4 y , p. 219. B . A . Nelson, E. J . Hodges and J . I . Simon, J . Org. Chem.,  102.  |1,  798  (l94l).  (1956).  ~  103.  R. Z e l i n s k i and K. Yorka, J . Org. Chem., 2 3 ,  104.  L. J . Bellamy, The I n f r a r e d Spectra o f Complex M o l e c u l e s , Methuen and Co. L t d . , London, 1958,  (1958).  225.  105.  J . Davo 11,  106.  R. P a u l , Compt. rend., 198,  107.  R. P. Z e l i n s k i , N. G. Peterson and H. R. W a l l n e r , J . Am. Chem. S o c , 7 4 , 1504 ( 1 9 5 2 ) . W. A. Bonner, Advances In Carbohydrate Chem., 6, 251 ( 1 9 5 1 ) ; Met hoar* i n uarbonydrate unemistry, Vu\L. I I , ed. by R. L. w n i s t l e r and H. h. woirrom, New York, Academic P r e s s , 1963, p. 4 6 5 . J . Houben and K. F u h r e r , Ber., 40, 4990 ( 1 9 0 7 ) .  108.  109.  J . Chem. S o c ,  2526  p.  640  375  (1949). (1934).  - 194 110.  C. P a a l and F. H o r n s t e i n , Ber., 3 9 , 1361  (1906).  111.  E. F i s c h e r and K. Hess, B e r . , 4 5 , 912 ( 1 9 1 2 ) .  112.  C. 0 . Jeremlas and C. A. Mackenzie, J . Am, Chem. S o c , 7 0 , 3920 ( 1 9 4 8 ) . ' :  113.  C D . Hurd and W. A. Bonner, J . Am, Chem, S o c , 6 7 , 1972 ( 1 9 4 5 ) .  ~  '  =  114.  W. A. Bonner, J . Am, Chem, Soc,, 6 8 , 1711  115.  C D . Hurd and W. A. Bonner, J , Am, Chem. S o c , 6 7 , 1664 ( 1 9 4 5 ) . — J . Yoshimura, N. Maramatsu and T. Sato, Nippon Kagaka Z a s s h l , 7 9 , 1503 ( 1 9 5 8 ) .  116.  (1946).  117.  E. V i s c h e r and T. R e i c h s t e i n , H e l v . Chim, Acta, 27, 1332 ( 1 9 4 4 ) . : =  118.  K. Freudenberg and K. Raschlg, Ber., 6 0 , 1633 ( 1 9 2 7 ) .  119.  R. C. Hockett and M. L. Downing, J . Am. Chem, S o c , 64, 2463 ( 1 9 4 2 ) . : "  120.  H. Ohle and E. Dickhauser, Ber., 5 8 , 2593 ( 1 9 2 5 ) .  121.  K. G a t z l and T. R e i c h s t e i n , H e l v . Chim. A c t a , 21, 914 (1938). =  122.  A. Rosenthal and H. J . Koch, Can, J . Chem., 42, 2025 (1964). * =  123.  R. U. Lemieux, R. K. K u l l n l g , H. J . B e r n s t e i n and W. G. Schneider, J , Am, Chem. S o c , 8 0 , 6098 (1958).  124.  M. K a r p l u s , J . Am. Chem. S o c , 8 5 , 2870 ( 1 9 6 3 ) .  125.  J . A. Pople, W. G. S c h e i d e r and H. J . B e r n s t e i n , High R e s o l u t i o n Magnetic Resonance, McGraw-Hill Book company, i n c . , New YorK, 1 9 5 9 , P. 1 3 2 .  126.  P. K. W. Woo, H. W. Dion and L. F. Johnson, J , |jm, Chem. Soc,  84, 1066 ( 1 9 6 2 ) .  127.  L . D. H a l l , Advances i n Carbohydrate Chem., 1 9 , i n p r e s s .  128.  R. U. Lemieux and J . Howard, Can, J , Chem., 4 l , 393 ( 1 9 6 3 ) .  129.  R. U. Lemieux and S. L e v i n e , Can. J . Chem., 42, 1473 (1964).  -  195' -  130.  R. U. Lemieux and J . W. Lown, Can. J . Chem., 42, 893 (1964). =  131.  R . J . Abraham, R. Freeman, L. D. H a l l and K. A. McLauchlan, J . Chem. S o c , 2080 ( 1 9 6 2 ) .  132.  R. A. E d i n g t o n , E. L. H i r s t and E . E. P e r c i v a l , J . Chem. S o c , 2281 ( 1 9 5 5 ) .  133.  P. A. Levene and R. S. T i p s o n , J . B i o l . Chem., 9 3 , 631 (1931). =  13**.  F. J . Bates and A s s o c i a t e s , " P o l a r i m e t r y , Sa c char-* met r y and the Sugars", Nat. B u r . Standard C i r c u l a r C44o ( 1 9 4 2 ) , P. 5 3 2 . =  135.  R. C r i e g e e , L . K r a f t  136.  J . W. P r a t t , N. K. Richtmyer and C. S. Hudson, J . Am.  and B. Rank, Ann., 507, 159 ( 1 9 3 3 ) .  Chem. S o c , 7*V, 2200 ( 1 9 5 2 ) . 137.  J . Honeyman and C. J . G. Shaw, J . Chem. S o c , 2454 ( 1 9 5 9 ) .  138.  S. J . Ahgyal and C. G. Macdonald, J . Chem. S o c , 686 (1952). R. J . Abraham, L. D. H a l l , L. Hough and K. A. McLauchlan, Chem. and Ind., 213 (1962)1 J . Chem. S o c , 3699 ( 1 9 6 2 ) .  139. 140.  R. TJ. Lemieux, J . D. Stevens and R. R. F r a s e r , Can. J . Chem., 40, 1955 ( 1 9 6 2 ) .  141.  A."B. F o s t e r , W. G. Overend, M. Stacey and L. F. Wiggins, J . Chem. S o c , 2542 ( 1 9 4 9 ) .  142.  J . A. M i l l s , Advances i n Carbohydrate Chem., 1 0 , 1 ( 1 9 5 5 ) .  143.  A. T. Ness, R. M. Hann and C. S. Hudson, J . Am. Chem. Soc., 66, 1901 ( 1 9 4 4 ) . R. M. Hann and C. S. Hudson, J . Am. Chem. S o c , 6 7 , 602 (1945) . ==  144. 145.  W. T.'Raskins, R. M. Hann and C. S. Hudson, J . Am. Chem. S o c , 6 5 , 67 (1943) .  146.  J . C. Sowden, Advances i n Carbohydrate Chem., 6 , 291 (1951). =  147.  H. Ledderhose, Z. p h y s i o l .  Chem., 4 , 139  (1880).  148.  B. C. B e r a , A. B. P o s t e r and M. Stacey, J , Chem. S o c ,  3.49.  S. Akiya and T. Osawa, J . Pharm. S o c Japan, 74, 1259  150.  P. A. Levene and P. B. LaPorge, J . B i o l . Chem., 2 1 ,  4531  (1956).  (1954).  345,  351 ( 1 9 1 5 ) .  —  *  —  151.  P. A. Levene, J , B i o l , Chem., 3 9 , 6 9 ,  152.  J . C. Sowden and M. T. O f t e d a h l , Methods i n Carbohydrate Chemistry, V o l . I , ed. by R. L. W h i s t l e r and M. L. woirrom, New York, Academic P r e s s , 1962, p. 2 3 5 .  153.  A. B. Grant, New Zealand J . S c l , Techno!., 3 7 , 509 ( 1 9 5 6 ) .  154.  Reference 104, p. 2 9 9 .  155.  A. Rosenthal and H. J . Koch, unpublished  156.  A. Camerman and J . T r o t t e r , Acta C r y s t . , i n p r e s s .  157.  M. Somogyi, J , B i o l , Chem., 16Q, 69 ( 1 9 4 5 ) .  158.  R. E . J . M I t c h e l , B . S c T h e s i s , U n i v e r s i t y o f B r i t i s h Columbia ( 1 9 6 3 ) .  159.  Reference 7 9 , p. 6 2 .  160.  R. L. S h r i n e r , R. C. Fuson and D. Y. C u r t i n , Systematic I d e n t i f i c a t i o n o f Organic Compounds, 4 t h Ed., Mew York, John Wiley and Sons, 1956, p. 9 8 .  161.  D. Y. C u r t i n , J . A. Gourse, W. A. Richardson and K. L. R i n e h a r t , J . O r g , Chem,, 24, 93 ( 1 9 5 9 ) .  162.  V. R. Mattox and E. C. K e n d a l l , J . Am. Chem. S o c , 70, 882 (1948) J J , B i o l . Chem., 188, 287 ( 1 9 b D .  163.  M. L. Wolfrom, J , Am, Chem, S o c , 5 3 , 2275 (1931) .  164.  M. L. Wolfrom and W. M. Morgan, J , Am. Chem, S o c , 54*  3390 ( 1 9 3 2 ) . 165.  results.  —  N. Kornblum, W. J . Jones and G. J . Anderson, J . Am. Chem.  Soc, 166.  (1919).  8 1 , 4113;-(1959).  K. E. P f l t z n e r and J . G. M o f f a t t , J , Am, Chem, S o c , 8 5 ,  (1963).  —  - 197 167.  D. H. R. B a r t o n , B. J . Garner and R. H. Wightman, J . Chem. S o c , 1 8 5 5 ( 1 9 6 4 ) .  168.  G. Henseke and G. Hanlsch, Angew. Chemle, 7 5 , 4 2 0 ( 1 9 6 3 ) .  

Cite

Citation Scheme:

    

Usage Statistics

Country Views Downloads
Romania 7 0
China 6 5
United States 3 1
Poland 1 0
France 1 0
Germany 1 0
Turkey 1 0
City Views Downloads
Unknown 10 0
Beijing 4 0
Ashburn 3 0
Shenzhen 2 5
Cologne 1 0

{[{ mDataHeader[type] }]} {[{ month[type] }]} {[{ tData[type] }]}
Download Stats

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0062109/manifest

Comment

Related Items